JACOB: A Study of Pertuzumab in Combination With Trastuzumab and Chemotherapy in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Metastatic Gastroesophageal Junction or Gastric Cancer
Sponsor
Hoffmann-La Roche (Industry)
Overall Status
Completed
CT.gov ID
NCT01774786
Collaborator
(none)
780
172
2
78.7
4.5
0.1
Study Details
Study Description
Brief Summary
This double-blind, placebo-controlled, randomized, multicenter, international, parallel arm study will evaluate the efficacy and safety of pertuzumab in combination with trastuzumab, fluoropyrimidine and cisplatin as first-line treatment in participants with HER2-positive metastatic gastroesophageal junction (GEJ) or gastric cancer (GC). Participants will be randomized to receive pertuzumab 840 milligrams (mg) or placebo intravenously every 3 weeks (q3w) in combination with trastuzumab (initial dose of 8 milligrams per kilogram [mg/kg] intravenously [IV] followed by 6 mg/kg IV q3w) and cisplatin and fluoropyrimidine (capecitabine or 5-fluorouracil) for the first 6 treatment cycles. Participants will continue to receive pertuzumab or placebo and trastuzumab until disease progression occurrence of unacceptable toxicity or withdrawal from the study for another reason.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
780 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
A Double-Blind, Placebo-Controlled, Randomized, Multicenter Phase III Study Evaluating the Efficacy and Safety of Pertuzumab in Combination With Trastuzumab and Chemotherapy in Patients With HER2-Positive Metastatic Gastroesophageal Junction and Gastric Cancer
Actual Study Start Date
:
Jun 10, 2013
Actual Primary Completion Date
:
Dec 9, 2016
Actual Study Completion Date
:
Dec 31, 2019
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Pertuzumab + Trastuzumab + Chemotherapy Participants will receive pertuzumab in combination with trastuzumab and chemotherapy (cisplatin and fluoropyrimidine [capecitabine or 5-fluorouracil]) for the first 6 treatment cycles (cycle length = 21 days). Thereafter, participants will continue to receive pertuzumab and trastuzumab until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason. |
Drug: 5-Fluorouracil
Participants will receive 5-fluorouracil 800 milligrams per meter square (mg/m^2)/24 hour IV infusion for 120 hours (Days 1-5) q3w for 6 cycles.
Drug: Capecitabine
Participants will receive capecitabine 1000 mg/m^2 orally twice daily, evening of Day 1 to morning of Day 15 (28 doses) q3w for 6 cycles.
Other Names:
Drug: Cisplatin
Participants will receive cisplatin 80 mg/m^2 IV q3w for 6 cycles.
Drug: Pertuzumab
Participants will receive pertuzumab 840 mg IV q3w until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason.
Other Names:
Drug: Trastuzumab
Participants will receive 8 mg/kg IV initial dose on Day 1, followed by 6 mg/kg IV q3w until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason.
Other Names:
|
| Placebo Comparator: Placebo + Trastuzumab + Chemotherapy Participants will receive placebo in combination with trastuzumab and chemotherapy (cisplatin and fluoropyrimidine [capecitabine or 5-fluorouracil]) for the first 6 treatment cycles (cycle length = 21 days). Thereafter, participants will continue to receive placebo and trastuzumab until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason. |
Drug: 5-Fluorouracil
Participants will receive 5-fluorouracil 800 milligrams per meter square (mg/m^2)/24 hour IV infusion for 120 hours (Days 1-5) q3w for 6 cycles.
Drug: Capecitabine
Participants will receive capecitabine 1000 mg/m^2 orally twice daily, evening of Day 1 to morning of Day 15 (28 doses) q3w for 6 cycles.
Other Names:
Drug: Cisplatin
Participants will receive cisplatin 80 mg/m^2 IV q3w for 6 cycles.
Drug: Placebo
Participants will receive placebo (matched to pertuzumab) IV q3w until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason.
Drug: Trastuzumab
Participants will receive 8 mg/kg IV initial dose on Day 1, followed by 6 mg/kg IV q3w until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Overall Survival [From Baseline until death from any cause (Median [full range] duration of follow-up in Pertuzumab vs. Placebo arms for Primary Analysis: 24.4 [0-42] months vs. 25.0 [0-41] months; Final Analysis: 46.1 [0-70] months vs. 44.4 [0-68] months)]
Overall survival (OS) was defined as the time from randomization to death from any cause. For participants who were still alive on the date of clinical data cut-off for the OS analysis, the last date when the participant was known to be alive on, or prior to the clinical cut-off date, was used to determine the censoring date. Participants who did not have any post-baseline data (e.g., dosing records, imaging dates, visit dates) were censored at the date of randomization plus 1 day.
Secondary Outcome Measures
- Progression-Free Survival, as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Criteria [Baseline to death or progressive disease (PD), whichever occurred first (Median [full range] duration of follow-up in Pertuzumab vs. Placebo arms for Primary Analysis: 24.9 [0-41] vs. 21.3 [0-39] months; Final Analysis: 50.4 [0-70] vs. 47.4 [0-66] months)]
Progression-free survival (PFS) is defined as the time from randomization to the first occurrence of progressive disease (PD), as determined by the investigator using RECIST v1.1, or death from any cause, whichever occurred first. Tumor assessments with CT or MRI scans of the chest, abdomen, and pelvis were performed every 9 weeks. Participants without documented PD or death were censored at the tumor assessment date for which the participant was last known to be progression-free. Participants who did not have any post-baseline tumor assessment data were censored at the date of randomization plus 1 day. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline; an absolute increase of at least 5 millimeters (mm) in the sum of diameters of target lesions; the appearance of one or more new lesions.
- Primary Analysis of the Percentage of Participants With Overall Objective Response, as Determined by the Investigator According to RECIST v1.1 Criteria [Baseline up to death or progressive disease, whichever occurred first (Median [full range] duration of follow-up in Pertuzumab vs. Placebo arms for Primary Analysis: 24.9 [0-41] months vs. 21.3 [0-39] months)]
The overall objective response rate was defined as the percentage of participants with partial response (PR) or complete response (CR) occurring on two consecutive occasions ≥4 weeks apart, as determined by the investigator using RECIST v1.1. Tumor assessments with computed tomography (CT) or magnetic resonance imaging (MRI) scans of the chest, abdomen, and pelvis were performed every 9 weeks. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. CR: disappearance of all target lesions. Measurable disease is defined as tumor lesions measured in at least one dimension (longest diameter in plane of measurement) with a minimum size of: 10 mm by CT or MRI scan; 10 mm caliper measurement by clinical examination; 20 mm by chest X-ray. For a malignant lymph node to be considered pathologically enlarged and measurable, it must be greater than or equal to (≥) 15 mm in short axis when assessed by CT scan.
- Final Analysis of the Percentage of Participants With Overall Objective Response, as Determined by the Investigator According to RECIST v1.1 Criteria [Baseline up to death or progressive disease, whichever occurred first (Median [full range] duration of follow-up in Pertuzumab vs. Placebo arms for Final Analysis: 50.4 [0-70] months vs. 47.4 [0-66] months)]
The overall objective response rate was defined as the percentage of participants with partial response (PR) or complete response (CR) occurring on two consecutive occasions ≥4 weeks apart, as determined by the investigator using RECIST v1.1. Tumor assessments with computed tomography (CT) or magnetic resonance imaging (MRI) scans of the chest, abdomen, and pelvis were performed every 9 weeks. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. CR: disappearance of all target lesions. Measurable disease is defined as tumor lesions measured in at least one dimension (longest diameter in plane of measurement) with a minimum size of: 10 mm by CT or MRI scan; 10 mm caliper measurement by clinical examination; 20 mm by chest X-ray. For a malignant lymph node to be considered pathologically enlarged and measurable, it must be greater than or equal to (≥) 15 mm in short axis when assessed by CT scan.
- Duration of Objective Response, as Determined by Investigator According to RECIST v1.1 Criteria [Baseline to death or progressive disease (PD), whichever occurred first (Median [full range] duration of follow-up in Pertuzumab vs. Placebo arms for Primary Analysis: 24.9 [0-41] vs. 21.3 [0-39] months; Final Analysis: 50.4 [0-70] vs. 47.4 [0-66] months)]
Duration of objective response is defined as the time from first occurrence of documented objective response to documented disease progression, as determined by the investigator using RECIST v1.1, or death from any cause. Objective response: PR or CR occurring on 2 consecutive occasions ≥4 weeks apart. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. CR: disappearance of all target lesions. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline; an absolute increase of at least 5 mm in the sum of diameters of target lesions; the appearance of one or more new lesions. Measurable disease defined as tumor lesions with a minimum size of: 10 mm by CT or MRI scan; 10 mm caliper measurement by clinical examination; 20 mm by chest X-ray. For a malignant lymph node, it must be ≥15 mm in short axis when assessed by CT scan.
- Percentage of Participants With Clinical Benefit, as Determined by the Investigator According to RECIST v1.1 Criteria [Baseline up to death or progressive disease, whichever occurred first (Median [full range] duration of follow-up in Pertuzumab vs. Placebo arms for Primary Analysis: 24.9 [0-41] months vs. 21.3 [0-39] months)]
The clinical benefit rate was defined as best response of complete response (CR) or partial response (PR) or stable disease (SD) for 6 weeks or longer, as determined by the investigator using RECIST v1.1. CR: disappearance of all target lesions. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression, taking as reference the smallest sum diameters while on study. Measurable disease is defined as tumor lesions measured in at least one dimension (longest diameter in plane of measurement) with a minimum size of: 10 mm by CT or MRI scan; 10 mm caliper measurement by clinical examination; 20 mm by chest X-ray. For a malignant lymph node to be considered pathologically enlarged and measurable, it must be >/=15 mm in short axis when assessed by CT scan. The clinical benefit rate was not updated at the final analysis.
- Overview of Safety: Number of Participants With at Least One Adverse Event, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 4.03 [From Baseline until end of post-treatment follow-up (up to 70 months)]
An adverse event (AE) is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. The investigator graded all AEs for severity per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 4.03; if not listed, the AE was assessed as follows: Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening/disabling; Grade 5 = death. The investigator determined whether an AE was related to study drug and independently assessed severity and seriousness of each AE.
- Number of Participants With Symptomatic or Asymptomatic Left Ventricular Systolic Dysfunction (LVSD) [From Baseline until end of post-treatment follow-up (up to 70 months)]
The number and percentage of participants with symptomatic left ventricular systolic dysfunction (LVSD) and asymptomatic LVSD events (defined as a left ventricular ejection fraction [LVEF] ≥10% decrease from baseline to an absolute value <50%) at any time during the study was summarized by treatment arm.
- Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score [Day 1 of each 21-day treatment cycle up to 28 and 60-90 days (post-treatment [PT] monitoring visits 1 and 2, respectively) after Day 1 of last treatment cycle (up to approximately 3.5 years)]
The EORTC QLQ-C30 included global health status, functional scales (physical, role, emotional, cognitive, and social), symptom scales (fatigue, nausea/vomiting, and pain) and single items (dyspnoea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Most questions used a 4-point scale (1 'Not at all' to 4 'Very much'; 2 questions used 7-point scale [1 'very poor' to 7 'Excellent']). Scores were averaged and transformed to 0 - 100 scale, whereby higher scores indicate greater functioning, greater quality of life, or a greater degree of symptoms, with changes of 5 - 10 points considered to be a minimally important difference to participants. A positive value means an increase, while a negative value means a decrease, in score at the indicated time-point relative to the score at baseline (Cycle 1, Day 1).
- Change From Baseline in EORTC QLQ-Gastric Cancer Module (EORTC QLQ-STO22) Score [Day 1 of each 21-day treatment cycle up to 28 and 60-90 days (post-treatment [PT] monitoring visits 1 and 2, respectively) after Day 1 of last treatment cycle (up to approximately 3.5 years)]
The EORTC QLQ-STO22 is a gastric cancer quality of life questionnaire. There are 22 questions concerning disease, treatment related symptoms, side effects, dysphagia, nutritional aspects, and questions about the emotional problems of gastric cancer (dysphagia, pain, reflux, eating restrictions, anxiety, dry mouth, body image, and hair loss). The questions are grouped into five scales and 4 single items which are related to the symptoms of the disease. Most questions used 4-point scale (1 'Not at all' to 4 'Very much'; 1 question was a yes or no answer). A linear transformation was used to standardize all scores and single-items to a scale of 0 to 100; higher score=better level of functioning or greater degree of symptoms. A positive value means an increase, while a negative values means a decrease, in score at the indicated time-point relative to the score at baseline (Cycle 1, Day 1).
- Maximum Serum Concentration (Cmax) of Pertuzumab [Post-dose (0.5 hour after end of 30-60 minutes infusion) on Day 1 of Cycles 1, 2, 4, and 8 (1 cycle = 21 days)]
- Cmax of Trastuzumab [Post-dose (0.5 hour after end of 30-60 minutes infusion) on Day 1 of Cycles 1, 2, 4, and 8 (1 cycle = 21 days)]
- Minimum Serum Concentration (Cmin) of Pertuzumab [Pre-dose (0-6 hours before infusion) on Day 1 of Cycles 1, 2, 3, 4, 6, and 8 (1 cycle = 21 days)]
- Cmin of Trastuzumab [Pre-dose (0-6 hours before infusion) on Day 1 of Cycles 1, 2, 3, 4, 6, and 8 (1 cycle = 21 days)]
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Histologically confirmed metastatic adenocarcinoma of the stomach or GEJ
-
Measurable or evaluable non-measurable disease as assessed by the investigator according to RECIST v1.1 criteria
-
Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
-
Life expectancy greater than equal to (>/=) 3 months
Exclusion Criteria:
-
Previous cytotoxic chemotherapy for advanced (metastatic) disease
-
Evidence of disease progression documented within 6 months after completion of prior neoadjuvant or adjuvant cytotoxic chemotherapy, or both, or radiotherapy for GEJ adenocarcinoma
-
Previous treatment with any HER2-directed therapy, at any time, for any duration
-
Previous exposure to any investigational treatment within 30 days before the first dose of study treatment
-
Radiotherapy within 30 days before the first dose of study treatment (within 2 weeks if given as palliation to bone metastases, if recovered from all toxicities)
-
History or evidence of brain metastases
-
Clinically significant active gastrointestinal (GI) bleeding (Grade >/=2 according to National Cancer Institute [NIC]-Common Terminology Criteria for Adverse Events Version 4.0 [CTCAEv.4.0])
-
Residual toxicity resulting from previous therapy (for example, hematologic, cardiovascular, or neurologic toxicity that is Grade >/=2). Alopecia is permitted
-
Other malignancy (in addition to gastric cancer [GC]) within 5 years before enrollment, except for carcinoma in situ of the cervix or squamous or basal cell carcinoma of the skin that has been previously treated with curative intent
-
Inadequate hematologic, renal or liver function
-
Pregnant or lactating women
-
History of congestive heart failure of any New York Heart Association (NYHA) criteria
-
Angina pectoris requiring treatment
-
Myocardial infarction within the past 6 months before the first dose of study drug
-
Clinically significant valvular heart disease or uncontrollable high-risk cardiac arrhythmia
-
History or evidence of poorly controlled hypertension
-
Baseline left ventricular ejection fraction (LVEF) value less than (<) 55 percent (%)
-
Any significant uncontrolled intercurrent systemic illness
-
Positive for hepatitis B, hepatitis C or human immunodeficiency virus (HIV) infection
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Florida Cancer Specialists - SCRI; Pharmacy | Fort Myers | Florida | United States | 33901 |
| 2 | University Of Chicago Medical Center; Section Of Hematology/Oncology | Chicago | Illinois | United States | 60637 |
| 3 | Indiana University Health; Goshen Center for Cancer Care | Goshen | Indiana | United States | 46526 |
| 4 | Comprehensive Cancer Centers of Nevada - Eastern Avenue | Las Vegas | Nevada | United States | 89169 |
| 5 | New York Oncology Hematology, P.C. | Albany | New York | United States | 12206 |
| 6 | Queens Medical Associates | Fresh Meadows | New York | United States | 11366 |
| 7 | Weill Medical College of Cornell University; Division of Hematology & Medical Oncology | New York | New York | United States | 10065 |
| 8 | Oncology Hematology Care | Cincinnati | Ohio | United States | 45219 |
| 9 | Medical University of South Carolina; Hollings Cancer Center | Charleston | South Carolina | United States | 29425 |
| 10 | Tennessee Oncology PLLC - Nashville (20th Ave) | Nashville | Tennessee | United States | 37203 |
| 11 | Royal Brisbane Womens Hosp; Division of Oncology | Herston | Queensland | Australia | 4029 |
| 12 | Monash Medical Centre; Oncology | Clayton | Victoria | Australia | 3168 |
| 13 | Austin Health; Cancer Clinical Trial Centre | Heidelberg | Victoria | Australia | 3084 |
| 14 | Sir Charles Gairdner Hospital; Medical Oncology | Perth | Western Australia | Australia | 6009 |
| 15 | Lkh Salzburg - Univ. Klinikum Salzburg; Iii. Medizinische Abt. | Salzburg | Austria | 5020 | |
| 16 | Krankenhaus St. Vinzenz Der Barmherzigen Schwestern Zams; Abt. Für Innere Medizin | Zams | Austria | 6511 | |
| 17 | Cliniques Universitaires St-Luc | Bruxelles | Belgium | 1200 | |
| 18 | Clinicas Oncologicas Integradas - COI | Rio De Janeiro | RJ | Brazil | 22290-160 |
| 19 | Hospital Nossa Senhora da Conceicao | Porto Alegre | RS | Brazil | 91350-200 |
| 20 | Hospital das Clinicas - UFRGS | Porto Alegre | RS | Brazil | |
| 21 | Centro de Pesquisas Oncologicas - CEPON | Florianopolis | SC | Brazil | 88034-000 |
| 22 | Hospital Sirio Libanes; Centro de Oncologia | Sao Paulo | SP | Brazil | 01308-050 |
| 23 | Clinica de Oncologia Medica | Sao Paulo | SP | Brazil | 01406100 |
| 24 | Hospital A. C. Camargo; Oncologia | Sao Paulo | SP | Brazil | 01509-010 |
| 25 | Universidade Federal de Sao Paulo - UNIFESP*X | Sao Paulo | SP | Brazil | 22793-080 |
| 26 | Complex Oncological Center - Plovdiv, EOOD | Plovdiv | Bulgaria | 4004 | |
| 27 | MHAT Serdika | Sofia | Bulgaria | 1301 | |
| 28 | SHATOD Dr. Marko Antonov Markov-Varna, EOOD; Department of Medicinall Onchotherapy and Palliative | Varna | Bulgaria | 9010 | |
| 29 | Hamilton Health Sciences - Juravinski Cancer Centre | Hamilton | Ontario | Canada | L8V 5C2 |
| 30 | London Regional Cancer Centre | London | Ontario | Canada | N6A 4L6 |
| 31 | Health Sciences North | Sudbury | Ontario | Canada | P3E 5J1 |
| 32 | Toronto East General Hospital; Haematology/Oncology | Toronto | Ontario | Canada | M4C 3E7 |
| 33 | Sunnybrook Health Science Centre | Toronto | Ontario | Canada | M4N 3M5 |
| 34 | Mount Sinai Hospital; Oncology | Toronto | Ontario | Canada | M5G 1X5 |
| 35 | McGill University; Glen Site; Oncology | Montreal | Quebec | Canada | H4A 3J1 |
| 36 | Cancer Hospital Chinese Academy of Medical Sciences. | Beijing | China | 100021 | |
| 37 | The Affiliated Hospital of Military Medical Sciences(The 307th Hospital of Chinese PLA) | Beijing | China | 100071 | |
| 38 | Beijing Cancer Hospital | Beijing | China | 100142 | |
| 39 | the First Hospital of Jilin University | Changchun | China | 130021 | |
| 40 | Jilin Cancer Hospital | Changchun | China | 132013 | |
| 41 | Changzhou First People's Hospital | Changzhou | China | 213003 | |
| 42 | Third Affiliated Hospital of Third Military Medical University | ChongQing | China | 400042 | |
| 43 | Fuzhou General Hospital, PLA Nanjing Military Area Command | Fuzhou | China | 110016 | |
| 44 | Sun Yet-sen University Cancer Center | Guangzhou | China | 510060 | |
| 45 | Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University | Hangzhou | China | 310016 | |
| 46 | Harbin Medical University Cancer Hospital | Harbin | China | 150081 | |
| 47 | The 1st Affiliated Hospital of Nanchang Unversity | Nanchang | China | 330006 | |
| 48 | The 81st Hospital of P.L.A. | Nanjing City | China | 210002 | |
| 49 | Affiliated Hospital of Nantong University | Nantong | China | 226001 | |
| 50 | Zhongshan Hospital Fudan University | Shanghai | China | 200032 | |
| 51 | Fudan University Shanghai Cancer Center | Shanghai | China | 200120 | |
| 52 | General Hospital of Shenyang Military Command of PLA | Shenyang | China | 110016 | |
| 53 | Hebei Medical University Fourth Hospital;(Tumor Hospital of Hebei Province) | Shijiazhuang | China | 050035 | |
| 54 | The First Affiliated Hospital of The Fourth Military Medical University (Xijing Hospital) | Xi'an | China | 710032 | |
| 55 | The Affiliated Hospital of Xuzhou Medical College | Xuzhou | China | 221000 | |
| 56 | Henan Cancer Hospital | Zhengzhou | China | 450008 | |
| 57 | The First Affiliated Hospital of Zhengzhou University | Zhengzhou | China | 450052 | |
| 58 | Clinical Hospital Centre Zagreb | Zagreb | Croatia | 10000 | |
| 59 | Clinical Hospital Sisters of Mercy | Zagreb | Croatia | 10000 | |
| 60 | Hospital Oncologia; Oncology | Salvador | El Salvador | 01101 | |
| 61 | Docrates Cance Center | Helsinki | Finland | 00180 | |
| 62 | Turku Uni Central Hospital; Oncology Clinics | Turku | Finland | 20520 | |
| 63 | Charité-Universitätsm. Berlin; Med. Klinik mit Schwerpunkt Hämatologie, Onkologie und Tumorimmunolo. | Berlin | Germany | 10117 | |
| 64 | Universitätsklinikum Essen; Innere Klinik und Poliklinik für Tumorforschung | Essen | Germany | 45122 | |
| 65 | Kliniken Essen-Mitte, Evang. Huyssens-Stiftung, Klinik für Internistische Onkologie / Haematologie | Essen | Germany | 45136 | |
| 66 | Klinik Esslingen; Klinik für Allgemeine Innere Medizin, Onkologie/Haematologie | Esslingen | Germany | 73730 | |
| 67 | Universitätsklinikum Hamburg-Eppendorf; Hubertus Wald Tumorzentrum | Hamburg | Germany | 20246 | |
| 68 | Universitaetsklinikum Leipzig, Universitaeres Krebszentrum Leipzig (UCCL) | Leipzig | Germany | 04103 | |
| 69 | Klinikum Ludwigsburg; Studiensekretariat | Ludwigsburg | Germany | 71640 | |
| 70 | Universitätsmedizin der Johannes Gutenberg-Universität Mainz; II. Medizinische Klinik | Mainz | Germany | 55131 | |
| 71 | Universitätsklinikum Mannheim, Tagestherapiezentrum, Interdisziplinäres Tumorzentrum | Mannheim | Germany | 68167 | |
| 72 | Philipps-Universität Marburg; Klinik für Innere Med.; Schwerpunkt Hämatologie/Onkologie/Immunologie | Marburg | Germany | 35043 | |
| 73 | Universitätsklinikum Ulm; Zentrum für Innere Medizin Klinik für Innere Medizin I | Ulm | Germany | 89081 | |
| 74 | Medical Solution; Hematology | Guatemala | Guatemala | 01-010 | |
| 75 | Semmelweis Egyetem Onkologiai Központ | Budapest | Hungary | 1083 | |
| 76 | Orszagos Onkologiai Intezet; B Belgyogyaszati Osztaly | Budapest | Hungary | 1122 | |
| 77 | Debreceni Egyetem, Klinikai Kozpont, Onkologiai Klinika | Debrecen | Hungary | 4032 | |
| 78 | Borsod-Abauj-Zemplen Megyei Korhaz es Egyetemi Oktato Korhaz;Sugarterapias Klinikai Onkologiai Intez | Miskolc | Hungary | 3526 | |
| 79 | Szegedi Tudomanyegyetem, AOK, Szent-Gyorgyi Albert Klinikai Kozpont, Onkoterapias Klinika | Szeged | Hungary | 6720 | |
| 80 | Seconda Universita' Degli Studi; Divsione Di Oncologia Medica | Napoli | Campania | Italy | 80131 |
| 81 | Azienda Ospedaliero-Universitaria S.Orsola-Malpighi; Unità Operativa Oncologia Medica | Bologna | Emilia-Romagna | Italy | 40138 |
| 82 | AUSL - IRCCS Santa Maria Nuova; U.O. Day Hospital di Oncologia | Reggio Emilia | Emilia-Romagna | Italy | 42100 |
| 83 | Azienda Ospedaliero-Universitaria Dipartimento Interaziendale Di Oncologia | Udine | Friuli-Venezia Giulia | Italy | 33100 |
| 84 | Policlinico Universitario Agostino Gemelli | Roma | Lazio | Italy | 00168 |
| 85 | Asst Papa Giovanni XXIII; Oncologia Medica | Bergamo | Lombardia | Italy | 24127 |
| 86 | Irccs Ospedale San Raffaele | Milano | Lombardia | Italy | 20132 |
| 87 | Irccs Istituto Europeo Di Oncologia (IEO); Oncologia Medica | Milano | Lombardia | Italy | 20141 |
| 88 | Ospedali Riuniti Di Ancona; Oncology | Ancona | Marche | Italy | 60121 |
| 89 | Ospedale Casa Sollievo Della Sofferenza IRCCS | San Giovanni Rotondo | Puglia | Italy | 71013 |
| 90 | Azlenda Ospendaliero-Universitaria Pisana; C.O. Oncologia 2 | Pisa | Toscana | Italy | 56100 |
| 91 | Ospedale Misericordia E Dolce; Oncologia Medica | Prato | Toscana | Italy | 59100 |
| 92 | Aichi Cancer Center Hospital; Clinical Oncology | Aichi | Japan | 464-8681 | |
| 93 | Nagoya university Hospital; Gastroenterological Surgery 2 | Aichi | Japan | 466-8560 | |
| 94 | National Cancer Center Hospital East; Gastroenterology | Chiba | Japan | 277-8577 | |
| 95 | National Hospital Organization Shikoku Cancer Center; Gastroenterology | Ehime | Japan | 791-0280 | |
| 96 | Kyushu University Hospital; Surgery and Science | Fukuoka | Japan | 812-8582 | |
| 97 | Gifu University Hospital; Digestive Surgery | Gifu | Japan | 501-1194 | |
| 98 | Hiroshima City Hiroshima Citizens Hospital; Surgery | Hiroshima | Japan | 730-8518 | |
| 99 | Kobe city Medical center General Hospital; Medical Oncology | Hyogo | Japan | 650-0047 | |
| 100 | St.Marianna University School of Medicine hospital; Medical Oncology | Kanagawa | Japan | 216-8511 | |
| 101 | Kanagawa Cancer Center; Gastrointestinal Surgery | Kanagawa | Japan | 241-8515 | |
| 102 | Osaka International Cancer Institute;; Medical oncology and Gastrointestinal oncology | Osaka | Japan | 541-8567 | |
| 103 | Osaka General Medical Center; Gastroenterological Surgery | Osaka | Japan | 558-8558 | |
| 104 | Saitama Cancer Center; Gastroenterology | Saitama | Japan | 362-0806 | |
| 105 | National Cancer Center Hospital; Gastrointestinal Oncology | Tokyo | Japan | 104-0045 | |
| 106 | Toyama University Hospital;Gastroenterology and Hematology | Toyama | Japan | 930-0194 | |
| 107 | Kazakh Scientific Research Institution Of Oncology and Radiology; Chemotherapy department | Almaty | Kazakhstan | 050022 | |
| 108 | Kyungpook National University Medical Center | Daegu | Korea, Republic of | 41404 | |
| 109 | Samsung Medical Center | Seoul | Korea, Republic of | (0)6351 | |
| 110 | Seoul National Uni Hospital; Dept. of Internal Medicine/Hematology/Oncology | Seoul | Korea, Republic of | 03080 | |
| 111 | Yonsei Medical Center; Dept. of Medicine , Division of Hemato-Oncology | Seoul | Korea, Republic of | 03722 | |
| 112 | Asan Medical Center; Medical Oncology | Seoul | Korea, Republic of | 05505 | |
| 113 | Seoul St Mary's Hospital | Seoul | Korea, Republic of | 06591 | |
| 114 | Hospital Universiti Sains Malaysia [Neurology] | Kubang Kerian | Kelantan | Malaysia | 16150 |
| 115 | Hospital Kuala Lumpur; Jabatan Radioterapi dan Onkologi | Kuala Lumpur | Malaysia | 50586 | |
| 116 | University Malaya Medical Centre; Clinical Oncology Unit, | Kuala Lumpur | Malaysia | 59100 | |
| 117 | Hospital Wanita dan Kanak-Kanak Sabah | Sabah | Malaysia | 88996 | |
| 118 | Hospital Angeles Metropolitano; Room 220 | Mexico City | Mexico CITY (federal District) | Mexico | 06760 |
| 119 | Inst. Nacional de Cancerologia; Investigacion Clinica | Mexico City | Mexico | 14000 | |
| 120 | Oaxaca Site Management Organization | Oaxaca | Mexico | 68000 | |
| 121 | Academisch Medisch Centrum Universiteit Amsterdam | Amsterdam | Netherlands | 1105 AZ | |
| 122 | Clinical Hospital; Oncology Department | Bitola | North Macedonia | 7000 | |
| 123 | University Clinic for Radiotherapy and Oncology | Skopje | North Macedonia | 1000 | |
| 124 | Medical Research Centre | Panama | Panama | ||
| 125 | Centro Medico Monte Carmelo | Arequipa | Peru | 04001 | |
| 126 | Hospital Sabogal; Oncology | Callao | Peru | 02 | |
| 127 | Hosp Nacion Edgardo Rebagliati; Oncologia Medica | Jesus Maria | Peru | Lima 11 | |
| 128 | Clinica Internacional, Sede San Borja; Unidad de Investigacion de Clínica Internacional | Lima | Peru | Lima 41 | |
| 129 | Clinica San Borja | Lima | Peru | Lima 41 | |
| 130 | Bialostockie Ctr Onkologii; Oddzial Chemioterapii Dziennej | Bialystok | Poland | 15-027 | |
| 131 | Szpital Specjalistyczny Podkarpacki Ośrodek Onkologiczny | Brzozów | Poland | 36-200 | |
| 132 | Centrum Onkologii;Im. Franciszka Lukaszczyka;Onkologii | Bydgoszcz | Poland | 85-796 | |
| 133 | Szpital Uniwersytecki w Krakowie, Oddział Kliniczny Kliniki Onkologii | Kraków | Poland | 30-688 | |
| 134 | SPZOZ Opolskie Centrum Onkologii im. Prof. Tadeusza Koszarawskiego | Opole | Poland | 45-060 | |
| 135 | NZOZ Centrum Medyczne HCP Sp. z o.o. | Poznan | Poland | 61-485 | |
| 136 | Wojewódzki Szpital Specjalistyczny Nr 3 | Rybnik | Poland | 44-200 | |
| 137 | Narodowy Instytut Onkologii im. M. Sklodowskiej-Curie; Klinika Gastroenterologii Onkologicznej | Warszawa | Poland | 02-781 | |
| 138 | Cardiomed Medical Center | Cluj-Napoca | Romania | 400015 | |
| 139 | Oncology Center Sf. Nectarie | Craiova | Romania | 200347 | |
| 140 | Euroclinic Center of Oncology SRL | Iasi | Romania | 700106 | |
| 141 | Clinical Oncology Dispensary of Ministry of Health of Tatarstan | Kazan | Russian Federation | 420029 | |
| 142 | Clinical Oncology Dispensary; Chemotherapy | Omsk | Russian Federation | 644013 | |
| 143 | SBI for HPE "Ryazan State Medical University n.a. I.P. Pavlov" of MoH of RF | Ryazan | Russian Federation | 390011 | |
| 144 | SBI of Healthcare Samara Regional Clinical Oncology Dispensary | Samara | Russian Federation | 443031 | |
| 145 | Hospital General Universitario de Elche; Servicio de Oncologia | Elche | Alicante | Spain | 03203 |
| 146 | Hospital Universitari Germans Trias i Pujol; Servicio de Oncologia | Badalona | Barcelona | Spain | 08916 |
| 147 | Hospital Universitario Reina Sofia; Servicio de Oncologia | Córdoba | Cordoba | Spain | 14004 |
| 148 | Hospital del Mar; Servicio de Oncologia | Barcelona | Spain | 08003 | |
| 149 | Hospital Univ Vall d'Hebron; Servicio de Oncologia | Barcelona | Spain | 08035 | |
| 150 | Hospital de la Santa Creu i Sant Pau; Servicio de Oncologia | Barcelona | Spain | 08041 | |
| 151 | Hospital Duran i Reynals; Oncologia | Barcelona | Spain | 08907 | |
| 152 | Hospital Ramon y Cajal; Servicio de Oncologia | Madrid | Spain | 28034 | |
| 153 | Hospital Universitario 12 de Octubre; Servicio de Oncologia | Madrid | Spain | 28041 | |
| 154 | CHUV; Departement d'Oncologie | Lausanne | Switzerland | 1011 | |
| 155 | Luzerner Kantonsspital; Medizinische Onkologie | Luzern | Switzerland | 6004 | |
| 156 | Taichung Veterans General Hospital; Dept of Surgery | Taichung | Taiwan | 407 | |
| 157 | National Cheng Kung University Hospital; Oncology | Tainan | Taiwan | 00704 | |
| 158 | Taipei Veterans General Hospital | Taipei City | Taiwan | 112 | |
| 159 | National Taiwan Uni Hospital; Dept of Oncology | Taipei | Taiwan | 100 | |
| 160 | Chang Gung Medical Foundation - Linkou; Division of Hematology- Oncology | Taoyuan | Taiwan | 333 | |
| 161 | Rajavithi Hospital; Division of Medical Oncology | Bangkok | Thailand | 10400 | |
| 162 | Ramathibodi Hospital; Dept of Med.-Div. of Med. Onc | Bangkok | Thailand | 10400 | |
| 163 | Faculty of Med. Siriraj Hosp.; Med.-Div. of Med. Oncology | Bangkok | Thailand | 10700 | |
| 164 | Khonkaen Hospital | Khonkaen | Thailand | 40000 | |
| 165 | Songklanagarind Hospital; Department of Oncology | Songkhla | Thailand | 90110 | |
| 166 | Ankara Uni School of Medicine; Medical Oncology | Ankara | Turkey | 06590 | |
| 167 | Akdeniz University Medical Faculty; Medical Oncology Department | Antalya | Turkey | 07070 | |
| 168 | Trakya University Medical Faculty Research And Practice Hospital Medical Oncology Department | Edirne | Turkey | 22770 | |
| 169 | Ataturk University Medical Faculty Yakutiye Research Hospital Medical Oncology Department | Erzurum | Turkey | 25240 | |
| 170 | Istanbul Uni Cerrahpasa Medical Faculty Hospital; Medical Oncology | Istanbul | Turkey | 34300 | |
| 171 | TC Necmettin Erbakan University Meram Medical Faculty Hospital | Konya | Turkey | 42080 | |
| 172 | Inonu University Medical Faculty Turgut Ozal Medical Center Medical Oncology Department | Malatya | Turkey | 44280 |
Sponsors and Collaborators
- Hoffmann-La Roche
Investigators
- Study Director: Clinical Trials, Hoffmann-La Roche
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01774786
Other Study ID Numbers:
- BO25114
- 2012-003554-83
First Posted:
Jan 24, 2013
Last Update Posted:
Dec 30, 2020
Last Verified:
Dec 1, 2020
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | A total of 780 participants were enrolled in the study. |
| Arm/Group Title | Pertuzumab + Trastuzumab + Chemotherapy | Placebo + Trastuzumab + Chemotherapy |
|---|---|---|
| Arm/Group Description | Participants received pertuzumab in combination with trastuzumab and chemotherapy (cisplatin and fluoropyrimidine [capecitabine or 5-fluorouracil]) for the first 6 treatment cycles (cycle length = 21 days). Thereafter, participants continued to receive pertuzumab and trastuzumab until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason. | Participants received placebo in combination with trastuzumab and chemotherapy (cisplatin and fluoropyrimidine [capecitabine or 5-fluorouracil]) for the first 6 treatment cycles (cycle length = 21 days). Thereafter, participants continued to receive placebo and trastuzumab until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason. |
| Period Title: Overall Study | ||
| STARTED | 388 | 392 |
| Did Not Receive Any Study Treatment | 4 | 3 |
| Received at Least One Dose of Pertuzumab | 384 | 1 |
| Received Placebo (No Pertuzumab) | 0 | 388 |
| COMPLETED | 60 | 46 |
| NOT COMPLETED | 328 | 346 |
Baseline Characteristics
| Arm/Group Title | Pertuzumab + Trastuzumab + Chemotherapy | Placebo + Trastuzumab + Chemotherapy | Total |
|---|---|---|---|
| Arm/Group Description | Participants received pertuzumab in combination with trastuzumab and chemotherapy (cisplatin and fluoropyrimidine [capecitabine or 5-fluorouracil]) for the first 6 treatment cycles (cycle length = 21 days). Thereafter, participants continued to receive pertuzumab and trastuzumab until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason. | Participants received placebo in combination with trastuzumab and chemotherapy (cisplatin and fluoropyrimidine [capecitabine or 5-fluorouracil]) for the first 6 treatment cycles (cycle length = 21 days). Thereafter, participants continued to receive placebo and trastuzumab until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason. | Total of all reporting groups |
| Overall Participants | 388 | 392 | 780 |
| Age (Years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [Years] |
60.9
(11.3)
|
60.1
(10.7)
|
60.5
(11.0)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
94
24.2%
|
69
17.6%
|
163
20.9%
|
| Male |
294
75.8%
|
323
82.4%
|
617
79.1%
|
| Geographic Region (Count of Participants) | |||
| Asia (excluding Japan) |
143
36.9%
|
146
37.2%
|
289
37.1%
|
| Japan |
40
10.3%
|
40
10.2%
|
80
10.3%
|
| North America/Western Europe/Australia |
133
34.3%
|
133
33.9%
|
266
34.1%
|
| South America/Eastern Europe |
72
18.6%
|
73
18.6%
|
145
18.6%
|
| Prior Gastrectomy (Count of Participants) | |||
| Prior Gastrectomy |
105
27.1%
|
102
26%
|
207
26.5%
|
| No Prior Gastrectomy |
283
72.9%
|
290
74%
|
573
73.5%
|
| Human Epidermal Growth Factor Receptor 2 (HER2) Status (Count of Participants) | |||
| IHC 2+/ISH+ |
129
33.2%
|
130
33.2%
|
259
33.2%
|
| IHC 3+ |
259
66.8%
|
262
66.8%
|
521
66.8%
|
| Measurability of Disease, per RECIST v1.1 (Count of Participants) | |||
| Measurable Disease |
351
90.5%
|
352
89.8%
|
703
90.1%
|
| Non-Measurable Evaluable Disease Only |
37
9.5%
|
40
10.2%
|
77
9.9%
|
Outcome Measures
| Title | Overall Survival |
|---|---|
| Description | Overall survival (OS) was defined as the time from randomization to death from any cause. For participants who were still alive on the date of clinical data cut-off for the OS analysis, the last date when the participant was known to be alive on, or prior to the clinical cut-off date, was used to determine the censoring date. Participants who did not have any post-baseline data (e.g., dosing records, imaging dates, visit dates) were censored at the date of randomization plus 1 day. |
| Time Frame | From Baseline until death from any cause (Median [full range] duration of follow-up in Pertuzumab vs. Placebo arms for Primary Analysis: 24.4 [0-42] months vs. 25.0 [0-41] months; Final Analysis: 46.1 [0-70] months vs. 44.4 [0-68] months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The intent-to-treat (ITT) population included all randomized participants, regardless of whether study medication was received. |
| Arm/Group Title | Pertuzumab + Trastuzumab + Chemotherapy | Placebo + Trastuzumab + Chemotherapy |
|---|---|---|
| Arm/Group Description | Participants received pertuzumab in combination with trastuzumab and chemotherapy (cisplatin and fluoropyrimidine [capecitabine or 5-fluorouracil]) for the first 6 treatment cycles (cycle length = 21 days). Thereafter, participants continued to receive pertuzumab and trastuzumab until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason. | Participants received placebo in combination with trastuzumab and chemotherapy (cisplatin and fluoropyrimidine [capecitabine or 5-fluorouracil]) for the first 6 treatment cycles (cycle length = 21 days). Thereafter, participants continued to receive placebo and trastuzumab until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason. |
| Measure Participants | 388 | 392 |
| Primary Analysis |
17.5
|
14.2
|
| Final Analysis |
18.1
|
14.2
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Pertuzumab + Trastuzumab + Chemotherapy, Placebo + Trastuzumab + Chemotherapy |
|---|---|---|
| Comments | Primary Analysis. The null hypothesis is that the survival distribution of OS is the same in the two treatment arms. | |
| Type of Statistical Test | Superiority | |
| Comments | The study was designed to have 80% power to show a significant difference with respect to the primary endpoint. | |
| Statistical Test of Hypothesis | p-Value | 0.0565 |
| Comments | The actual p-value significance threshold required for OS was 0.0455, after alpha spent at the interim analysis was taken into account. | |
| Method | Stratified Log-Rank | |
| Comments | Stratified analysis by geographic region, HER2 status, and prior gastrectomy. | |
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.84 | |
| Confidence Interval |
(2-Sided) 95% 0.71 to 1.00 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | HR was calculated as pertuzumab arm vs. placebo arm. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Pertuzumab + Trastuzumab + Chemotherapy, Placebo + Trastuzumab + Chemotherapy |
|---|---|---|
| Comments | Final Analysis | |
| Type of Statistical Test | Other | |
| Comments | Exploratory | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.85 | |
| Confidence Interval |
(2-Sided) 95% 0.72 to 0.99 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | HR was calculated as pertuzumab arm vs. placebo arm. Stratified analysis by geographic region, HER2 status, and prior gastrectomy. | |
| Title | Progression-Free Survival, as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Criteria |
|---|---|
| Description | Progression-free survival (PFS) is defined as the time from randomization to the first occurrence of progressive disease (PD), as determined by the investigator using RECIST v1.1, or death from any cause, whichever occurred first. Tumor assessments with CT or MRI scans of the chest, abdomen, and pelvis were performed every 9 weeks. Participants without documented PD or death were censored at the tumor assessment date for which the participant was last known to be progression-free. Participants who did not have any post-baseline tumor assessment data were censored at the date of randomization plus 1 day. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline; an absolute increase of at least 5 millimeters (mm) in the sum of diameters of target lesions; the appearance of one or more new lesions. |
| Time Frame | Baseline to death or progressive disease (PD), whichever occurred first (Median [full range] duration of follow-up in Pertuzumab vs. Placebo arms for Primary Analysis: 24.9 [0-41] vs. 21.3 [0-39] months; Final Analysis: 50.4 [0-70] vs. 47.4 [0-66] months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The ITT population included all randomized participants, regardless of whether study medication was received. |
| Arm/Group Title | Pertuzumab + Trastuzumab + Chemotherapy | Placebo + Trastuzumab + Chemotherapy |
|---|---|---|
| Arm/Group Description | Participants received pertuzumab in combination with trastuzumab and chemotherapy (cisplatin and fluoropyrimidine [capecitabine or 5-fluorouracil]) for the first 6 treatment cycles (cycle length = 21 days). Thereafter, participants continued to receive pertuzumab and trastuzumab until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason. | Participants received placebo in combination with trastuzumab and chemotherapy (cisplatin and fluoropyrimidine [capecitabine or 5-fluorouracil]) for the first 6 treatment cycles (cycle length = 21 days). Thereafter, participants continued to receive placebo and trastuzumab until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason. |
| Measure Participants | 388 | 392 |
| Primary Analysis |
8.5
|
7.0
|
| Final Analysis |
8.5
|
7.2
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Pertuzumab + Trastuzumab + Chemotherapy, Placebo + Trastuzumab + Chemotherapy |
|---|---|---|
| Comments | Primary Analysis | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.73 | |
| Confidence Interval |
(2-Sided) 95% 0.62 to 0.86 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | A stratified Cox proportional hazards regression model was used to estimate the HR between the pertuzumab arm vs. the placebo arm. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Pertuzumab + Trastuzumab + Chemotherapy, Placebo + Trastuzumab + Chemotherapy |
|---|---|---|
| Comments | Final Analysis | |
| Type of Statistical Test | Other | |
| Comments | Exploratory | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.73 | |
| Confidence Interval |
(2-Sided) 95% 0.62 to 0.85 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | A stratified Cox proportional hazards regression model was used to estimate the HR between the pertuzumab arm vs. the placebo arm. | |
| Title | Primary Analysis of the Percentage of Participants With Overall Objective Response, as Determined by the Investigator According to RECIST v1.1 Criteria |
|---|---|
| Description | The overall objective response rate was defined as the percentage of participants with partial response (PR) or complete response (CR) occurring on two consecutive occasions ≥4 weeks apart, as determined by the investigator using RECIST v1.1. Tumor assessments with computed tomography (CT) or magnetic resonance imaging (MRI) scans of the chest, abdomen, and pelvis were performed every 9 weeks. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. CR: disappearance of all target lesions. Measurable disease is defined as tumor lesions measured in at least one dimension (longest diameter in plane of measurement) with a minimum size of: 10 mm by CT or MRI scan; 10 mm caliper measurement by clinical examination; 20 mm by chest X-ray. For a malignant lymph node to be considered pathologically enlarged and measurable, it must be greater than or equal to (≥) 15 mm in short axis when assessed by CT scan. |
| Time Frame | Baseline up to death or progressive disease, whichever occurred first (Median [full range] duration of follow-up in Pertuzumab vs. Placebo arms for Primary Analysis: 24.9 [0-41] months vs. 21.3 [0-39] months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The subset of participants with measurable disease at baseline, according to RECIST v1.1 criteria. |
| Arm/Group Title | Pertuzumab + Trastuzumab + Chemotherapy | Placebo + Trastuzumab + Chemotherapy |
|---|---|---|
| Arm/Group Description | Participants received pertuzumab in combination with trastuzumab and chemotherapy (cisplatin and fluoropyrimidine [capecitabine or 5-fluorouracil]) for the first 6 treatment cycles (cycle length = 21 days). Thereafter, participants continued to receive pertuzumab and trastuzumab until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason. | Participants received placebo in combination with trastuzumab and chemotherapy (cisplatin and fluoropyrimidine [capecitabine or 5-fluorouracil]) for the first 6 treatment cycles (cycle length = 21 days). Thereafter, participants continued to receive placebo and trastuzumab until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason. |
| Measure Participants | 351 | 352 |
| Objective Response (CR + PR) |
56.7
14.6%
|
48.3
12.3%
|
| Complete Response (CR) |
5.1
1.3%
|
0.9
0.2%
|
| Partial Response (PR) |
51.6
13.3%
|
47.4
12.1%
|
| Stable Disease (SD) |
27.9
7.2%
|
33.0
8.4%
|
| Progressive Disease (PD) |
4.8
1.2%
|
8.0
2%
|
| Not Evaluable/Missing |
10.5
2.7%
|
10.8
2.8%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Pertuzumab + Trastuzumab + Chemotherapy, Placebo + Trastuzumab + Chemotherapy |
|---|---|---|
| Comments | Primary Analysis of Objective Response Rate | |
| Type of Statistical Test | Other | |
| Comments | Exploratory | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in Objective Response |
| Estimated Value | 8.40 | |
| Confidence Interval |
(2-Sided) 95% 0.89 to 15.91 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Difference in objective response was calculated as the pertuzumab arm minus placebo arm. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Pertuzumab + Trastuzumab + Chemotherapy, Placebo + Trastuzumab + Chemotherapy |
|---|---|---|
| Comments | Primary Analysis of Objective Response Rate | |
| Type of Statistical Test | Other | |
| Comments | Exploratory | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.40 | |
| Confidence Interval |
(2-Sided) 95% 1.04 to 1.89 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Odds ratio was calculated as the pertuzumab arm vs. placebo arm. | |
| Title | Final Analysis of the Percentage of Participants With Overall Objective Response, as Determined by the Investigator According to RECIST v1.1 Criteria |
|---|---|
| Description | The overall objective response rate was defined as the percentage of participants with partial response (PR) or complete response (CR) occurring on two consecutive occasions ≥4 weeks apart, as determined by the investigator using RECIST v1.1. Tumor assessments with computed tomography (CT) or magnetic resonance imaging (MRI) scans of the chest, abdomen, and pelvis were performed every 9 weeks. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. CR: disappearance of all target lesions. Measurable disease is defined as tumor lesions measured in at least one dimension (longest diameter in plane of measurement) with a minimum size of: 10 mm by CT or MRI scan; 10 mm caliper measurement by clinical examination; 20 mm by chest X-ray. For a malignant lymph node to be considered pathologically enlarged and measurable, it must be greater than or equal to (≥) 15 mm in short axis when assessed by CT scan. |
| Time Frame | Baseline up to death or progressive disease, whichever occurred first (Median [full range] duration of follow-up in Pertuzumab vs. Placebo arms for Final Analysis: 50.4 [0-70] months vs. 47.4 [0-66] months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The subset of participants with measurable disease at baseline, according to RECIST v1.1 criteria. |
| Arm/Group Title | Pertuzumab + Trastuzumab + Chemotherapy | Placebo + Trastuzumab + Chemotherapy |
|---|---|---|
| Arm/Group Description | Participants received pertuzumab in combination with trastuzumab and chemotherapy (cisplatin and fluoropyrimidine [capecitabine or 5-fluorouracil]) for the first 6 treatment cycles (cycle length = 21 days). Thereafter, participants continued to receive pertuzumab and trastuzumab until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason. | Participants received placebo in combination with trastuzumab and chemotherapy (cisplatin and fluoropyrimidine [capecitabine or 5-fluorouracil]) for the first 6 treatment cycles (cycle length = 21 days). Thereafter, participants continued to receive placebo and trastuzumab until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason. |
| Measure Participants | 351 | 352 |
| Objective Response (CR + PR) |
57.0
14.7%
|
48.6
12.4%
|
| Complete Response (CR) |
5.7
1.5%
|
2.0
0.5%
|
| Partial Response (PR) |
51.3
13.2%
|
46.6
11.9%
|
| Stable Disease (SD) |
27.6
7.1%
|
32.7
8.3%
|
| Progressive Disease (PD) |
4.8
1.2%
|
8.2
2.1%
|
| Not Evaluable/Missing |
10.5
2.7%
|
10.5
2.7%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Pertuzumab + Trastuzumab + Chemotherapy, Placebo + Trastuzumab + Chemotherapy |
|---|---|---|
| Comments | Final Analysis of Objective Response Rate | |
| Type of Statistical Test | Other | |
| Comments | Exploratory | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in Objective Response |
| Estimated Value | 8.40 | |
| Confidence Interval |
(2-Sided) 95% 0.89 to 15.91 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Difference in objective response was calculated as the pertuzumab arm minus placebo arm. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Pertuzumab + Trastuzumab + Chemotherapy, Placebo + Trastuzumab + Chemotherapy |
|---|---|---|
| Comments | Final Analysis of Objective Response Rate | |
| Type of Statistical Test | Other | |
| Comments | Exploratory | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.40 | |
| Confidence Interval |
(2-Sided) 95% 1.04 to 1.89 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Odds ratio was calculated as the pertuzumab arm vs. placebo arm. | |
| Title | Duration of Objective Response, as Determined by Investigator According to RECIST v1.1 Criteria |
|---|---|
| Description | Duration of objective response is defined as the time from first occurrence of documented objective response to documented disease progression, as determined by the investigator using RECIST v1.1, or death from any cause. Objective response: PR or CR occurring on 2 consecutive occasions ≥4 weeks apart. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. CR: disappearance of all target lesions. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline; an absolute increase of at least 5 mm in the sum of diameters of target lesions; the appearance of one or more new lesions. Measurable disease defined as tumor lesions with a minimum size of: 10 mm by CT or MRI scan; 10 mm caliper measurement by clinical examination; 20 mm by chest X-ray. For a malignant lymph node, it must be ≥15 mm in short axis when assessed by CT scan. |
| Time Frame | Baseline to death or progressive disease (PD), whichever occurred first (Median [full range] duration of follow-up in Pertuzumab vs. Placebo arms for Primary Analysis: 24.9 [0-41] vs. 21.3 [0-39] months; Final Analysis: 50.4 [0-70] vs. 47.4 [0-66] months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The participants with measurable disease at baseline who achieved a documented objective response, according to RECIST v1.1 criteria. |
| Arm/Group Title | Pertuzumab + Trastuzumab + Chemotherapy | Placebo + Trastuzumab + Chemotherapy |
|---|---|---|
| Arm/Group Description | Participants received pertuzumab in combination with trastuzumab and chemotherapy (cisplatin and fluoropyrimidine [capecitabine or 5-fluorouracil]) for the first 6 treatment cycles (cycle length = 21 days). Thereafter, participants continued to receive pertuzumab and trastuzumab until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason. | Participants received placebo in combination with trastuzumab and chemotherapy (cisplatin and fluoropyrimidine [capecitabine or 5-fluorouracil]) for the first 6 treatment cycles (cycle length = 21 days). Thereafter, participants continued to receive placebo and trastuzumab until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason. |
| Measure Participants | 200 | 171 |
| Primary Analysis |
10.2
|
8.4
|
| Final Analysis |
10.2
|
8.4
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Pertuzumab + Trastuzumab + Chemotherapy, Placebo + Trastuzumab + Chemotherapy |
|---|---|---|
| Comments | Primary Analysis | |
| Type of Statistical Test | Other | |
| Comments | Exploratory | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.82 | |
| Confidence Interval |
(2-Sided) 95% 0.64 to 1.06 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | HR was calculated as pertuzumab arm vs. placebo arm. Stratified analysis by geographic region, HER2 status, and prior gastrectomy. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Pertuzumab + Trastuzumab + Chemotherapy, Placebo + Trastuzumab + Chemotherapy |
|---|---|---|
| Comments | Final Analysis | |
| Type of Statistical Test | Other | |
| Comments | Exploratory | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.78 | |
| Confidence Interval |
(2-Sided) 95% 0.62 to 0.98 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | HR was calculated as pertuzumab arm vs. placebo arm. Stratified analysis by geographic region, HER2 status, and prior gastrectomy. | |
| Title | Percentage of Participants With Clinical Benefit, as Determined by the Investigator According to RECIST v1.1 Criteria |
|---|---|
| Description | The clinical benefit rate was defined as best response of complete response (CR) or partial response (PR) or stable disease (SD) for 6 weeks or longer, as determined by the investigator using RECIST v1.1. CR: disappearance of all target lesions. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression, taking as reference the smallest sum diameters while on study. Measurable disease is defined as tumor lesions measured in at least one dimension (longest diameter in plane of measurement) with a minimum size of: 10 mm by CT or MRI scan; 10 mm caliper measurement by clinical examination; 20 mm by chest X-ray. For a malignant lymph node to be considered pathologically enlarged and measurable, it must be >/=15 mm in short axis when assessed by CT scan. The clinical benefit rate was not updated at the final analysis. |
| Time Frame | Baseline up to death or progressive disease, whichever occurred first (Median [full range] duration of follow-up in Pertuzumab vs. Placebo arms for Primary Analysis: 24.9 [0-41] months vs. 21.3 [0-39] months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The subset of participants with measurable disease at baseline, according to RECIST v1.1 criteria. |
| Arm/Group Title | Pertuzumab + Trastuzumab + Chemotherapy | Placebo + Trastuzumab + Chemotherapy |
|---|---|---|
| Arm/Group Description | Participants received pertuzumab in combination with trastuzumab and chemotherapy (cisplatin and fluoropyrimidine [capecitabine or 5-fluorouracil]) for the first 6 treatment cycles (cycle length = 21 days). Thereafter, participants continued to receive pertuzumab and trastuzumab until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason. | Participants received placebo in combination with trastuzumab and chemotherapy (cisplatin and fluoropyrimidine [capecitabine or 5-fluorouracil]) for the first 6 treatment cycles (cycle length = 21 days). Thereafter, participants continued to receive placebo and trastuzumab until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason. |
| Measure Participants | 351 | 352 |
| Number (95% Confidence Interval) [percentage of participants] |
84.6
21.8%
|
81.3
20.7%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Pertuzumab + Trastuzumab + Chemotherapy, Placebo + Trastuzumab + Chemotherapy |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | Exploratory | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in Clinical Benefit Rate |
| Estimated Value | 3.37 | |
| Confidence Interval |
(2-Sided) 95% -2.34 to 9.07 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Difference in clinical benefit rate was calculated as the pertuzumab arm minus placebo arm. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Pertuzumab + Trastuzumab + Chemotherapy, Placebo + Trastuzumab + Chemotherapy |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | Exploratory | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.27 | |
| Confidence Interval |
(2-Sided) 95% 0.86 to 1.88 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Odds ratio was calculated as the pertuzumab arm vs. placebo arm. | |
| Title | Overview of Safety: Number of Participants With at Least One Adverse Event, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 4.03 |
|---|---|
| Description | An adverse event (AE) is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. The investigator graded all AEs for severity per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 4.03; if not listed, the AE was assessed as follows: Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening/disabling; Grade 5 = death. The investigator determined whether an AE was related to study drug and independently assessed severity and seriousness of each AE. |
| Time Frame | From Baseline until end of post-treatment follow-up (up to 70 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety population included all participants who received any amount of any study medication. Those who received any amount of pertuzumab were included in the pertuzumab arm; all other treated participants were included in the placebo arm. |
| Arm/Group Title | Pertuzumab + Trastuzumab + Chemotherapy | Placebo + Trastuzumab + Chemotherapy |
|---|---|---|
| Arm/Group Description | Participants received pertuzumab in combination with trastuzumab and chemotherapy (cisplatin and fluoropyrimidine [capecitabine or 5-fluorouracil]) for the first 6 treatment cycles (cycle length = 21 days). Thereafter, participants continued to receive pertuzumab and trastuzumab until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason. | Participants received placebo in combination with trastuzumab and chemotherapy (cisplatin and fluoropyrimidine [capecitabine or 5-fluorouracil]) for the first 6 treatment cycles (cycle length = 21 days). Thereafter, participants continued to receive placebo and trastuzumab until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason. |
| Measure Participants | 385 | 388 |
| Any Adverse Event (AE) |
381
98.2%
|
385
98.2%
|
| AE with Fatal Outcome |
27
7%
|
31
7.9%
|
| Serious AE |
178
45.9%
|
156
39.8%
|
| Grade 3-5 AE |
310
79.9%
|
288
73.5%
|
| AE Leading to Pertuz/Pbo & Trastuz Discontinuation |
48
12.4%
|
46
11.7%
|
| AE Leading to Dose Interruption &/or Dose Delay |
110
28.4%
|
94
24%
|
| Title | Number of Participants With Symptomatic or Asymptomatic Left Ventricular Systolic Dysfunction (LVSD) |
|---|---|
| Description | The number and percentage of participants with symptomatic left ventricular systolic dysfunction (LVSD) and asymptomatic LVSD events (defined as a left ventricular ejection fraction [LVEF] ≥10% decrease from baseline to an absolute value <50%) at any time during the study was summarized by treatment arm. |
| Time Frame | From Baseline until end of post-treatment follow-up (up to 70 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety population included all participants who received any amount of any study medication. Those who received any amount of pertuzumab were included in the pertuzumab arm; all other treated participants were included in the placebo arm. |
| Arm/Group Title | Pertuzumab + Trastuzumab + Chemotherapy | Placebo + Trastuzumab + Chemotherapy |
|---|---|---|
| Arm/Group Description | Participants received pertuzumab in combination with trastuzumab and chemotherapy (cisplatin and fluoropyrimidine [capecitabine or 5-fluorouracil]) for the first 6 treatment cycles (cycle length = 21 days). Thereafter, participants continued to receive pertuzumab and trastuzumab until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason. | Participants received placebo in combination with trastuzumab and chemotherapy (cisplatin and fluoropyrimidine [capecitabine or 5-fluorouracil]) for the first 6 treatment cycles (cycle length = 21 days). Thereafter, participants continued to receive placebo and trastuzumab until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason. |
| Measure Participants | 385 | 388 |
| Symptomatic LVSD |
3
0.8%
|
1
0.3%
|
| Asymptomatic LVSD |
20
5.2%
|
18
4.6%
|
| Title | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score |
|---|---|
| Description | The EORTC QLQ-C30 included global health status, functional scales (physical, role, emotional, cognitive, and social), symptom scales (fatigue, nausea/vomiting, and pain) and single items (dyspnoea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Most questions used a 4-point scale (1 'Not at all' to 4 'Very much'; 2 questions used 7-point scale [1 'very poor' to 7 'Excellent']). Scores were averaged and transformed to 0 - 100 scale, whereby higher scores indicate greater functioning, greater quality of life, or a greater degree of symptoms, with changes of 5 - 10 points considered to be a minimally important difference to participants. A positive value means an increase, while a negative value means a decrease, in score at the indicated time-point relative to the score at baseline (Cycle 1, Day 1). |
| Time Frame | Day 1 of each 21-day treatment cycle up to 28 and 60-90 days (post-treatment [PT] monitoring visits 1 and 2, respectively) after Day 1 of last treatment cycle (up to approximately 3.5 years) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the ITT population (includes all randomized participants, regardless of whether study medication was received) with both a baseline assessment and at least 1 post-treatment assessment are included in the analysis. |
| Arm/Group Title | Pertuzumab + Trastuzumab + Chemotherapy | Placebo + Trastuzumab + Chemotherapy |
|---|---|---|
| Arm/Group Description | Participants received pertuzumab in combination with trastuzumab and chemotherapy (cisplatin and fluoropyrimidine [capecitabine or 5-fluorouracil]) for the first 6 treatment cycles (cycle length = 21 days). Thereafter, participants continued to receive pertuzumab and trastuzumab until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason. | Participants received placebo in combination with trastuzumab and chemotherapy (cisplatin and fluoropyrimidine [capecitabine or 5-fluorouracil]) for the first 6 treatment cycles (cycle length = 21 days). Thereafter, participants continued to receive placebo and trastuzumab until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason. |
| Measure Participants | 388 | 392 |
| Appetite Loss: Cycle 1 (Baseline) |
26.68
(28.65)
|
27.59
(29.96)
|
| Appetite Loss: Change at Cycle 2 |
6.57
(33.18)
|
0.97
(35.86)
|
| Appetite Loss: Change at Cycle 3 |
3.63
(36.19)
|
3.81
(36.76)
|
| Appetite Loss: Change at Cycle 4 |
5.24
(34.20)
|
0.79
(34.33)
|
| Appetite Loss: Change at Cycle 5 |
4.55
(36.50)
|
2.90
(35.85)
|
| Appetite Loss: Change at Cycle 6 |
3.94
(36.07)
|
-0.39
(36.86)
|
| Appetite Loss: Change at Cycle 7 |
2.07
(38.05)
|
1.61
(35.98)
|
| Appetite Loss: Change at Cycle 8 |
-2.42
(33.81)
|
-3.69
(34.20)
|
| Appetite Loss: Change at Cycle 9 |
-6.67
(31.92)
|
-4.76
(31.67)
|
| Appetite Loss: Change at Cycle 10 |
-8.06
(32.52)
|
-6.63
(28.48)
|
| Appetite Loss: Change at Cycle 11 |
-9.36
(33.19)
|
-9.68
(27.38)
|
| Appetite Loss: Change at Cycle 12 |
-9.22
(33.73)
|
-9.05
(28.51)
|
| Appetite Loss: Change at Cycle 13 |
-10.17
(31.10)
|
-10.81
(29.18)
|
| Appetite Loss: Change at Cycle 14 |
-12.10
(31.96)
|
-12.09
(30.32)
|
| Appetite Loss: Change at Cycle 15 |
-8.21
(32.96)
|
-9.18
(29.81)
|
| Appetite Loss: Change at Cycle 16 |
-6.03
(33.07)
|
-10.59
(28.74)
|
| Appetite Loss: Change at Cycle 17 |
-6.55
(29.29)
|
-9.91
(29.05)
|
| Appetite Loss: Change at Cycle 18 |
-4.90
(31.25)
|
-14.08
(27.98)
|
| Appetite Loss: Change at Cycle 19 |
-8.33
(31.34)
|
-13.13
(28.57)
|
| Appetite Loss: Change at Cycle 20 |
-3.97
(31.65)
|
-13.23
(29.66)
|
| Appetite Loss: Change at Cycle 21 |
-5.91
(31.01)
|
-14.20
(32.76)
|
| Appetite Loss: Change at Cycle 22 |
-4.98
(34.45)
|
-16.31
(29.38)
|
| Appetite Loss: Change at Cycle 23 |
-6.35
(36.84)
|
-11.36
(35.90)
|
| Appetite Loss: Change at Cycle 24 |
-7.78
(33.82)
|
-13.33
(30.00)
|
| Appetite Loss: Change at Cycle 25 |
-7.05
(35.14)
|
-12.04
(31.02)
|
| Appetite Loss: Change at Cycle 26 |
-7.48
(34.87)
|
-12.50
(32.52)
|
| Appetite Loss: Change at Cycle 27 |
-10.08
(33.76)
|
-9.20
(28.03)
|
| Appetite Loss: Change at Cycle 28 |
-10.00
(32.20)
|
-11.54
(29.73)
|
| Appetite Loss: Change at PT Visit 1 |
7.30
(36.86)
|
2.64
(33.14)
|
| Appetite Loss: Change at PT Visit 2 |
-0.33
(33.83)
|
4.55
(34.53)
|
| Cognitive Functional Scale: Cycle 1 (Baseline) |
87.95
(17.32)
|
88.22
(16.18)
|
| Cognitive Functional Scale: Change at Cycle 2 |
-1.90
(17.82)
|
-1.81
(16.93)
|
| Cognitive Functional Scale: Change at Cycle 3 |
-0.83
(17.11)
|
-3.17
(18.30)
|
| Cognitive Functional Scale: Change at Cycle 4 |
-2.04
(17.78)
|
-2.99
(19.28)
|
| Cognitive Functional Scale: Change at Cycle 5 |
-3.04
(19.09)
|
-4.59
(19.59)
|
| Cognitive Functional Scale: Change at Cycle 6 |
-5.10
(19.23)
|
-3.84
(19.00)
|
| Cognitive Functional Scale: Change at Cycle 7 |
-4.34
(19.52)
|
-4.31
(19.09)
|
| Cognitive Functional Scale: Change at Cycle 8 |
-3.15
(17.90)
|
-3.30
(17.59)
|
| Cognitive Functional Scale: Change at Cycle 9 |
-2.22
(18.53)
|
-4.59
(18.53)
|
| Cognitive Functional Scale: Change at Cycle 10 |
-3.32
(19.44)
|
-3.11
(18.50)
|
| Cognitive Functional Scale: Change at Cycle 11 |
-2.83
(18.44)
|
-3.44
(17.06)
|
| Cognitive Functional Scale: Change at Cycle 12 |
-3.35
(20.00)
|
-2.52
(18.16)
|
| Cognitive Functional Scale: Change at Cycle 13 |
-1.79
(19.04)
|
-3.60
(17.89)
|
| Cognitive Functional Scale: Change at Cycle 14 |
-1.98
(19.00)
|
-2.29
(17.56)
|
| Cognitive Functional Scale: Change at Cycle 15 |
-1.15
(18.47)
|
-2.38
(16.05)
|
| Cognitive Functional Scale: Change at Cycle 16 |
-2.73
(17.16)
|
-2.55
(17.16)
|
| Cognitive Functional Scale: Change at Cycle 17 |
-2.53
(17.21)
|
-1.13
(15.44)
|
| Cognitive Functional Scale: Change at Cycle 18 |
-2.78
(18.18)
|
0.47
(16.42)
|
| Cognitive Functional Scale: Change at Cycle 19 |
-1.04
(18.07)
|
0.00
(14.62)
|
| Cognitive Functional Scale: Change at Cycle 20 |
-2.18
(19.67)
|
0.79
(15.68)
|
| Cognitive Functional Scale: Change at Cycle 21 |
-2.11
(20.56)
|
0.62
(16.50)
|
| Cognitive Functional Scale: Change at Cycle 22 |
-4.73
(18.98)
|
-0.71
(18.04)
|
| Cognitive Functional Scale: Change at Cycle 23 |
-2.38
(19.60)
|
1.14
(17.75)
|
| Cognitive Functional Scale: Change at Cycle 24 |
-2.78
(19.69)
|
1.25
(16.18)
|
| Cognitive Functional Scale: Change at Cycle 25 |
-5.45
(16.41)
|
-0.93
(18.66)
|
| Cognitive Functional Scale: Change at Cycle 26 |
-2.38
(16.32)
|
-1.56
(18.63)
|
| Cognitive Functional Scale: Change at Cycle 27 |
-3.88
(18.84)
|
-1.15
(18.33)
|
| Cognitive Functional Scale: Change at Cycle 28 |
-3.75
(15.78)
|
0.00
(20.00)
|
| Cognitive Functional Scale: Change at PT Visit 1 |
-9.13
(21.90)
|
-9.16
(20.02)
|
| Cognitive Functional Scale: Change at PT Visit 2 |
-8.42
(20.22)
|
-11.21
(22.48)
|
| Constipation Symptom Scale: Cycle 1 (Baseline) |
20.43
(28.45)
|
18.41
(27.13)
|
| Constipation Symptom Scale: Change at Cycle 2 |
-5.39
(27.05)
|
0.29
(27.23)
|
| Constipation Symptom Scale: Change at Cycle 3 |
-7.48
(28.98)
|
-2.11
(27.65)
|
| Constipation Symptom Scale: Change at Cycle 4 |
-5.32
(29.21)
|
-3.73
(28.26)
|
| Constipation Symptom Scale: Change at Cycle 5 |
-5.94
(29.15)
|
-1.28
(27.64)
|
| Constipation Symptom Scale: Change at Cycle 6 |
-7.13
(29.65)
|
-2.33
(30.24)
|
| Constipation Symptom Scale: Change at Cycle 7 |
-8.13
(30.11)
|
-4.09
(29.06)
|
| Constipation Symptom Scale: Change at Cycle 8 |
-8.05
(30.90)
|
-4.45
(27.32)
|
| Constipation Symptom Scale: Change at Cycle 9 |
-10.00
(27.10)
|
-5.61
(26.74)
|
| Constipation Symptom Scale: Change at Cycle 10 |
-9.32
(29.56)
|
-7.43
(26.81)
|
| Constipation Symptom Scale: Change at Cycle 11 |
-9.16
(29.60)
|
-6.88
(27.84)
|
| Constipation Symptom Scale: Change at Cycle 12 |
-10.27
(29.04)
|
-7.25
(25.39)
|
| Constipation Symptom Scale: Change at Cycle 13 |
-11.19
(29.55)
|
-5.76
(26.27)
|
| Constipation Symptom Scale: Change at Cycle 14 |
-11.60
(27.11)
|
-6.21
(26.00)
|
| Constipation Symptom Scale: Change at Cycle 15 |
-10.51
(26.59)
|
-7.14
(24.52)
|
| Constipation Symptom Scale: Change at Cycle 16 |
-8.62
(24.91)
|
-7.45
(25.39)
|
| Constipation Symptom Scale: Change at Cycle 17 |
-8.33
(24.30)
|
-5.86
(18.59)
|
| Constipation Symptom Scale: Change at Cycle 18 |
-7.52
(22.93)
|
-6.57
(26.20)
|
| Constipation Symptom Scale: Change at Cycle 19 |
-3.47
(25.81)
|
-3.03
(25.97)
|
| Constipation Symptom Scale: Change at Cycle 20 |
-3.97
(26.08)
|
-4.76
(26.68)
|
| Constipation Symptom Scale: Change at Cycle 21 |
-3.80
(29.23)
|
-9.26
(25.42)
|
| Constipation Symptom Scale: Change at Cycle 22 |
-4.98
(28.58)
|
-8.51
(27.34)
|
| Constipation Symptom Scale: Change at Cycle 23 |
-6.35
(28.62)
|
-8.33
(26.04)
|
| Constipation Symptom Scale: Change at Cycle 24 |
-7.78
(27.01)
|
-10.00
(26.37)
|
| Constipation Symptom Scale: Change at Cycle 25 |
-7.05
(29.77)
|
-9.26
(28.30)
|
| Constipation Symptom Scale: Change at Cycle 26 |
-6.12
(30.94)
|
-6.25
(23.09)
|
| Constipation Symptom Scale: Change at Cycle 27 |
-7.75
(28.95)
|
-10.34
(26.88)
|
| Constipation Symptom Scale: Change at Cycle 28 |
-6.67
(26.37)
|
-6.41
(21.12)
|
| Constipation Symptom Scale: Change at PT Visit 1 |
-6.78
(31.45)
|
-4.62
(26.19)
|
| Constipation Symptom Scale: Change at PT Visit 2 |
-6.93
(28.41)
|
-0.91
(31.11)
|
| Diarrhea Symptom Scale: Cycle 1 (Baseline) |
8.87
(17.70)
|
9.16
(18.87)
|
| Diarrhea Symptom Scale: Change at Cycle 2 |
15.12
(30.42)
|
5.20
(23.79)
|
| Diarrhea Symptom Scale: Change at Cycle 3 |
14.64
(27.71)
|
4.99
(26.10)
|
| Diarrhea Symptom Scale: Change at Cycle 4 |
14.13
(27.15)
|
4.63
(24.07)
|
| Diarrhea Symptom Scale: Change at Cycle 5 |
13.17
(25.47)
|
4.99
(23.70)
|
| Diarrhea Symptom Scale: Change at Cycle 6 |
14.81
(27.01)
|
2.47
(23.76)
|
| Diarrhea Symptom Scale: Change at Cycle 7 |
12.26
(23.74)
|
2.92
(23.44)
|
| Diarrhea Symptom Scale: Change at Cycle 8 |
8.91
(23.56)
|
2.61
(23.53)
|
| Diarrhea Symptom Scale: Change at Cycle 9 |
6.83
(23.76)
|
2.04
(21.25)
|
| Diarrhea Symptom Scale: Change at Cycle 10 |
6.63
(23.97)
|
0.60
(20.91)
|
| Diarrhea Symptom Scale: Change at Cycle 11 |
5.26
(21.80)
|
2.60
(20.36)
|
| Diarrhea Symptom Scale: Change at Cycle 12 |
3.98
(22.30)
|
1.92
(19.97)
|
| Diarrhea Symptom Scale: Change at Cycle 13 |
4.29
(24.27)
|
1.50
(19.27)
|
| Diarrhea Symptom Scale: Change at Cycle 14 |
3.95
(24.45)
|
0.98
(20.15)
|
| Diarrhea Symptom Scale: Change at Cycle 15 |
3.33
(23.79)
|
1.02
(19.42)
|
| Diarrhea Symptom Scale: Change at Cycle 16 |
5.46
(21.06)
|
3.14
(15.10)
|
| Diarrhea Symptom Scale: Change at Cycle 17 |
2.68
(21.05)
|
2.25
(14.94)
|
| Diarrhea Symptom Scale: Change at Cycle 18 |
3.59
(21.95)
|
3.29
(17.95)
|
| Diarrhea Symptom Scale: Change at Cycle 19 |
3.82
(19.86)
|
2.02
(16.41)
|
| Diarrhea Symptom Scale: Change at Cycle 20 |
5.95
(19.47)
|
3.70
(17.05)
|
| Diarrhea Symptom Scale: Change at Cycle 21 |
3.80
(23.26)
|
1.85
(16.40)
|
| Diarrhea Symptom Scale: Change at Cycle 22 |
6.97
(24.98)
|
4.26
(17.88)
|
| Diarrhea Symptom Scale: Change at Cycle 23 |
6.88
(21.72)
|
8.33
(20.49)
|
| Diarrhea Symptom Scale: Change at Cycle 24 |
7.22
(22.21)
|
3.33
(16.54)
|
| Diarrhea Symptom Scale: Change at Cycle 25 |
8.97
(23.91)
|
2.78
(14.64)
|
| Diarrhea Symptom Scale: Change at Cycle 26 |
5.44
(21.89)
|
5.21
(20.93)
|
| Diarrhea Symptom Scale: Change at Cycle 27 |
3.88
(22.07)
|
3.45
(16.29)
|
| Diarrhea Symptom Scale: Change at Cycle 28 |
7.50
(27.72)
|
2.56
(16.12)
|
| Diarrhea Symptom Scale: Change at PT Visit 1 |
8.14
(26.00)
|
1.98
(24.35)
|
| Diarrhea Symptom Scale: Change at PT Visit 2 |
7.26
(25.65)
|
4.24
(29.65)
|
| Dyspnoea Symptom Scale: Cycle 1 (Baseline) |
12.07
(17.99)
|
12.65
(20.20)
|
| Dyspnoea Symptom Scale: Change at Cycle 2 |
-0.50
(19.04)
|
0.29
(19.72)
|
| Dyspnoea Symptom Scale: Change at Cycle 3 |
-0.31
(20.18)
|
-0.32
(20.38)
|
| Dyspnoea Symptom Scale: Change at Cycle 4 |
1.23
(20.31)
|
1.81
(21.08)
|
| Dyspnoea Symptom Scale: Change at Cycle 5 |
2.58
(20.62)
|
1.39
(21.18)
|
| Dyspnoea Symptom Scale: Change at Cycle 6 |
3.20
(23.79)
|
0.39
(20.55)
|
| Dyspnoea Symptom Scale: Change at Cycle 7 |
0.00
(21.94)
|
0.59
(20.07)
|
| Dyspnoea Symptom Scale: Change at Cycle 8 |
-0.14
(21.99)
|
0.93
(20.56)
|
| Dyspnoea Symptom Scale: Change at Cycle 9 |
-1.12
(20.51)
|
0.17
(18.95)
|
| Dyspnoea Symptom Scale: Change at Cycle 10 |
-0.54
(21.56)
|
1.00
(16.99)
|
| Dyspnoea Symptom Scale: Change at Cycle 11 |
-2.16
(19.58)
|
-1.29
(17.77)
|
| Dyspnoea Symptom Scale: Change at Cycle 12 |
-2.53
(19.75)
|
-0.71
(18.95)
|
| Dyspnoea Symptom Scale: Change at Cycle 13 |
-1.43
(20.34)
|
-1.20
(16.77)
|
| Dyspnoea Symptom Scale: Change at Cycle 14 |
-1.98
(19.00)
|
-2.61
(17.98)
|
| Dyspnoea Symptom Scale: Change at Cycle 15 |
-2.84
(21.26)
|
2.72
(18.95)
|
| Dyspnoea Symptom Scale: Change at Cycle 16 |
-1.45
(20.42)
|
1.18
(18.86)
|
| Dyspnoea Symptom Scale: Change at Cycle 17 |
-1.82
(20.61)
|
0.90
(19.87)
|
| Dyspnoea Symptom Scale: Change at Cycle 18 |
-0.98
(20.15)
|
-2.35
(18.10)
|
| Dyspnoea Symptom Scale: Change at Cycle 19 |
-1.74
(20.73)
|
0.51
(18.15)
|
| Dyspnoea Symptom Scale: Change at Cycle 20 |
-1.19
(20.98)
|
-1.06
(16.90)
|
| Dyspnoea Symptom Scale: Change at Cycle 21 |
1.27
(22.29)
|
-0.62
(19.95)
|
| Dyspnoea Symptom Scale: Change at Cycle 22 |
-1.99
(22.38)
|
0.71
(14.73)
|
| Dyspnoea Symptom Scale: Change at Cycle 23 |
-1.59
(21.94)
|
1.52
(14.30)
|
| Dyspnoea Symptom Scale: Change at Cycle 24 |
1.11
(22.10)
|
-1.67
(12.96)
|
| Dyspnoea Symptom Scale: Change at Cycle 25 |
0.64
(21.38)
|
-3.70
(15.49)
|
| Dyspnoea Symptom Scale: Change at Cycle 26 |
0.00
(22.57)
|
1.04
(23.16)
|
| Dyspnoea Symptom Scale: Change at Cycle 27 |
0.78
(21.19)
|
3.45
(22.44)
|
| Dyspnoea Symptom Scale: Change at Cycle 28 |
1.67
(21.28)
|
3.85
(17.20)
|
| Dyspnoea Symptom Scale: Change at PT Visit 1 |
6.97
(26.98)
|
6.77
(23.82)
|
| Dyspnoea Symptom Scale: Change at PT Visit 2 |
3.30
(23.81)
|
9.39
(26.76)
|
| Emotional Functional Scale: Cycle 1 (Baseline) |
76.90
(20.21)
|
76.56
(19.84)
|
| Emotional Functional Scale: Change at Cycle 2 |
3.53
(16.84)
|
3.05
(18.49)
|
| Emotional Functional Scale: Change at Cycle 3 |
2.65
(18.63)
|
3.96
(19.95)
|
| Emotional Functional Scale: Change at Cycle 4 |
3.10
(21.11)
|
3.67
(20.44)
|
| Emotional Functional Scale: Change at Cycle 5 |
2.62
(19.97)
|
2.74
(21.72)
|
| Emotional Functional Scale: Change at Cycle 6 |
1.01
(19.64)
|
4.93
(21.00)
|
| Emotional Functional Scale: Change at Cycle 7 |
1.72
(21.09)
|
4.41
(20.18)
|
| Emotional Functional Scale: Change at Cycle 8 |
3.43
(20.66)
|
5.66
(19.63)
|
| Emotional Functional Scale: Change at Cycle 9 |
4.72
(20.10)
|
4.78
(19.45)
|
| Emotional Functional Scale: Change at Cycle 10 |
3.72
(21.76)
|
6.74
(18.13)
|
| Emotional Functional Scale: Change at Cycle 11 |
5.85
(19.64)
|
4.96
(19.21)
|
| Emotional Functional Scale: Change at Cycle 12 |
4.93
(21.38)
|
5.24
(19.14)
|
| Emotional Functional Scale: Change at Cycle 13 |
5.00
(23.07)
|
5.18
(17.95)
|
| Emotional Functional Scale: Change at Cycle 14 |
5.93
(22.90)
|
6.29
(19.03)
|
| Emotional Functional Scale: Change at Cycle 15 |
6.03
(22.13)
|
5.19
(19.61)
|
| Emotional Functional Scale: Change at Cycle 16 |
5.17
(23.20)
|
5.29
(20.81)
|
| Emotional Functional Scale: Change at Cycle 17 |
6.01
(23.55)
|
6.31
(18.70)
|
| Emotional Functional Scale: Change at Cycle 18 |
3.68
(24.11)
|
5.87
(19.39)
|
| Emotional Functional Scale: Change at Cycle 19 |
4.69
(26.01)
|
5.56
(18.68)
|
| Emotional Functional Scale: Change at Cycle 20 |
3.47
(26.92)
|
5.42
(17.91)
|
| Emotional Functional Scale: Change at Cycle 21 |
4.54
(26.55)
|
6.48
(22.00)
|
| Emotional Functional Scale: Change at Cycle 22 |
5.35
(28.67)
|
6.91
(18.66)
|
| Emotional Functional Scale: Change at Cycle 23 |
5.82
(28.42)
|
6.63
(21.00)
|
| Emotional Functional Scale: Change at Cycle 24 |
5.28
(26.22)
|
8.54
(19.57)
|
| Emotional Functional Scale: Change at Cycle 25 |
5.93
(25.48)
|
8.80
(20.89)
|
| Emotional Functional Scale: Change at Cycle 26 |
5.44
(27.77)
|
5.99
(16.15)
|
| Emotional Functional Scale: Change at Cycle 27 |
7.56
(28.34)
|
5.75
(18.51)
|
| Emotional Functional Scale: Change at Cycle 28 |
7.08
(25.43)
|
7.05
(18.96)
|
| Emotional Functional Scale: Change at PT Visit 1 |
-5.48
(23.16)
|
-3.92
(23.28)
|
| Emotional Functional Scale: Change at PT Visit 2 |
-2.64
(23.33)
|
-4.47
(23.34)
|
| Fatigue Symptom Scale: Cycle 1 (Baseline) |
31.96
(23.46)
|
32.27
(21.92)
|
| Fatigue Symptom Scale: Change at Cycle 2 |
3.13
(19.80)
|
2.32
(21.57)
|
| Fatigue Symptom Scale: Change at Cycle 3 |
1.41
(22.65)
|
3.19
(22.97)
|
| Fatigue Symptom Scale: Change at Cycle 4 |
2.77
(23.14)
|
1.58
(24.04)
|
| Fatigue Symptom Scale: Change at Cycle 5 |
3.87
(25.75)
|
3.05
(24.29)
|
| Fatigue Symptom Scale: Change at Cycle 6 |
4.37
(25.64)
|
2.62
(23.68)
|
| Fatigue Symptom Scale: Change at Cycle 7 |
2.36
(26.79)
|
0.97
(23.44)
|
| Fatigue Symptom Scale: Change at Cycle 8 |
-0.19
(25.00)
|
-1.18
(22.74)
|
| Fatigue Symptom Scale: Change at Cycle 9 |
-2.38
(22.69)
|
-2.01
(22.84)
|
| Fatigue Symptom Scale: Change at Cycle 10 |
-3.41
(24.69)
|
-3.08
(22.41)
|
| Fatigue Symptom Scale: Change at Cycle 11 |
-4.35
(22.66)
|
-3.44
(21.21)
|
| Fatigue Symptom Scale: Change at Cycle 12 |
-3.14
(24.56)
|
-4.60
(24.39)
|
| Fatigue Symptom Scale: Change at Cycle 13 |
-4.57
(23.31)
|
-4.50
(21.47)
|
| Fatigue Symptom Scale: Change at Cycle 14 |
-6.75
(24.32)
|
-6.54
(22.89)
|
| Fatigue Symptom Scale: Change at Cycle 15 |
-5.47
(24.68)
|
-4.99
(22.40)
|
| Fatigue Symptom Scale: Change at Cycle 16 |
-3.54
(24.81)
|
-6.93
(21.89)
|
| Fatigue Symptom Scale: Change at Cycle 17 |
-4.27
(25.50)
|
-3.45
(21.91)
|
| Fatigue Symptom Scale: Change at Cycle 18 |
-4.14
(24.42)
|
-8.92
(20.54)
|
| Fatigue Symptom Scale: Change at Cycle 19 |
-5.32
(27.83)
|
-9.01
(20.71)
|
| Fatigue Symptom Scale: Change at Cycle 20 |
-5.56
(26.64)
|
-6.53
(21.83)
|
| Fatigue Symptom Scale: Change at Cycle 21 |
-3.94
(25.97)
|
-7.41
(23.45)
|
| Fatigue Symptom Scale: Change at Cycle 22 |
-1.49
(25.58)
|
-10.64
(22.22)
|
| Fatigue Symptom Scale: Change at Cycle 23 |
-5.82
(25.23)
|
-9.60
(28.01)
|
| Fatigue Symptom Scale: Change at Cycle 24 |
-1.67
(27.05)
|
-12.50
(24.29)
|
| Fatigue Symptom Scale: Change at Cycle 25 |
-4.70
(26.16)
|
-12.35
(22.03)
|
| Fatigue Symptom Scale: Change at Cycle 26 |
-4.99
(24.85)
|
-11.46
(22.84)
|
| Fatigue Symptom Scale: Change at Cycle 27 |
-6.98
(23.76)
|
-5.36
(23.87)
|
| Fatigue Symptom Scale: Change at Cycle 28 |
-6.39
(18.98)
|
-4.70
(26.14)
|
| Fatigue Symptom Scale: Change at PT Visit 1 |
10.02
(28.48)
|
5.25
(24.00)
|
| Fatigue Symptom Scale: Change at PT Visit 2 |
7.70
(27.65)
|
9.70
(25.01)
|
| Financial Difficulties Scale: Cycle 1 (Baseline) |
26.67
(30.32)
|
26.21
(29.78)
|
| Financial Difficulties Scale: Change at Cycle 2 |
-0.90
(26.85)
|
-2.46
(25.46)
|
| Financial Difficulties Scale: Change at Cycle 3 |
0.31
(27.62)
|
0.00
(26.33)
|
| Financial Difficulties Scale: Change at Cycle 4 |
0.89
(25.95)
|
0.11
(25.10)
|
| Financial Difficulties Scale: Change at Cycle 5 |
1.75
(27.71)
|
2.58
(26.46)
|
| Financial Difficulties Scale: Change at Cycle 6 |
1.11
(27.62)
|
0.92
(26.36)
|
| Financial Difficulties Scale: Change at Cycle 7 |
1.11
(31.08)
|
0.30
(26.41)
|
| Financial Difficulties Scale: Change at Cycle 8 |
1.15
(30.21)
|
0.47
(25.27)
|
| Financial Difficulties Scale: Change at Cycle 9 |
1.11
(29.78)
|
-0.51
(24.75)
|
| Financial Difficulties Scale: Change at Cycle 10 |
0.90
(30.10)
|
-2.42
(24.30)
|
| Financial Difficulties Scale: Change at Cycle 11 |
0.39
(29.37)
|
-0.22
(24.84)
|
| Financial Difficulties Scale: Change at Cycle 12 |
-1.05
(28.91)
|
-0.97
(26.39)
|
| Financial Difficulties Scale: Change at Cycle 13 |
-0.95
(28.82)
|
0.30
(24.82)
|
| Financial Difficulties Scale: Change at Cycle 14 |
-1.73
(29.74)
|
-0.98
(25.02)
|
| Financial Difficulties Scale: Change at Cycle 15 |
-1.81
(28.96)
|
1.36
(26.18)
|
| Financial Difficulties Scale: Change at Cycle 16 |
-3.16
(30.13)
|
0.39
(25.97)
|
| Financial Difficulties Scale: Change at Cycle 17 |
-3.87
(29.59)
|
1.35
(27.28)
|
| Financial Difficulties Scale: Change at Cycle 18 |
-2.29
(27.46)
|
2.35
(26.02)
|
| Financial Difficulties Scale: Change at Cycle 19 |
-0.35
(28.41)
|
-0.51
(27.73)
|
| Financial Difficulties Scale: Change at Cycle 20 |
1.19
(29.47)
|
1.59
(27.71)
|
| Financial Difficulties Scale: Change at Cycle 21 |
1.27
(28.96)
|
-4.94
(27.78)
|
| Financial Difficulties Scale: Change at Cycle 22 |
2.49
(26.79)
|
-4.26
(23.69)
|
| Financial Difficulties Scale: Change at Cycle 23 |
-0.53
(26.43)
|
-2.27
(29.11)
|
| Financial Difficulties Scale: Change at Cycle 24 |
1.11
(24.52)
|
-5.83
(26.03)
|
| Financial Difficulties Scale: Change at Cycle 25 |
3.21
(27.42)
|
-4.63
(25.39)
|
| Financial Difficulties Scale: Change at Cycle 26 |
2.72
(28.74)
|
-2.22
(26.16)
|
| Financial Difficulties Scale: Change at Cycle 27 |
-3.10
(23.92)
|
1.15
(24.37)
|
| Financial Difficulties Scale: Change at Cycle 28 |
-1.67
(23.81)
|
-1.28
(24.00)
|
| Financial Difficulties Scale: Change at PT Visit 1 |
1.70
(29.66)
|
1.33
(26.21)
|
| Financial Difficulties Scale: Change at PT Visit 2 |
1.98
(26.17)
|
4.24
(31.32)
|
| Nausea and Vomiting Scale: Cycle 1 (Baseline) |
11.14
(19.11)
|
11.92
(18.76)
|
| Nausea And Vomiting Scale: Change at Cycle 2 |
5.85
(22.65)
|
4.08
(22.25)
|
| Nausea And Vomiting Scale: Change at Cycle 3 |
5.12
(23.62)
|
5.06
(21.14)
|
| Nausea And Vomiting Scale: Change at Cycle 4 |
4.10
(21.85)
|
3.56
(23.76)
|
| Nausea And Vomiting Scale: Change at Cycle 5 |
5.13
(22.58)
|
5.15
(23.81)
|
| Nausea And Vomiting Scale: Change at Cycle 6 |
4.11
(23.36)
|
2.59
(21.24)
|
| Nausea And Vomiting Scale: Change at Cycle 7 |
2.07
(23.58)
|
2.49
(22.31)
|
| Nausea And Vomiting Scale: Change at Cycle 8 |
-0.86
(20.80)
|
-0.77
(20.21)
|
| Nausea And Vomiting Scale: Change at Cycle 9 |
-2.54
(20.85)
|
-2.98
(19.78)
|
| Nausea And Vomiting Scale: Change at Cycle 10 |
-4.30
(18.81)
|
-2.81
(20.57)
|
| Nausea And Vomiting Scale: Change at Cycle 11 |
-3.51
(18.01)
|
-3.66
(20.04)
|
| Nausea And Vomiting Scale: Change at Cycle 12 |
-3.04
(18.07)
|
-3.45
(20.34)
|
| Nausea And Vomiting Scale: Change at Cycle 13 |
-4.02
(16.29)
|
-3.60
(19.25)
|
| Nausea And Vomiting Scale: Change at Cycle 14 |
-3.46
(19.54)
|
-5.72
(18.54)
|
| Nausea And Vomiting Scale: Change at Cycle 15 |
-3.59
(16.34)
|
-3.91
(16.55)
|
| Nausea And Vomiting Scale: Change at Cycle 16 |
-0.43
(20.32)
|
-2.55
(20.00)
|
| Nausea And Vomiting Scale: Change at Cycle 17 |
-0.60
(17.46)
|
-3.15
(16.48)
|
| Nausea And Vomiting Scale: Change at Cycle 18 |
-0.65
(16.90)
|
-3.52
(18.24)
|
| Nausea And Vomiting Scale: Change at Cycle 19 |
-0.87
(18.32)
|
-4.04
(19.62)
|
| Nausea And Vomiting Scale: Change at Cycle 20 |
-1.79
(18.48)
|
-3.97
(17.89)
|
| Nausea And Vomiting Scale: Change at Cycle 21 |
-1.05
(20.03)
|
-6.48
(19.80)
|
| Nausea And Vomiting Scale: Change at Cycle 22 |
-3.48
(19.14)
|
-8.16
(18.99)
|
| Nausea And Vomiting Scale: Change at Cycle 23 |
-4.23
(17.70)
|
-6.44
(24.70)
|
| Nausea And Vomiting Scale: Change at Cycle 24 |
-4.72
(16.26)
|
-7.92
(17.70)
|
| Nausea And Vomiting Scale: Change at Cycle 25 |
-4.17
(20.84)
|
-7.41
(19.29)
|
| Nausea And Vomiting Scale: Change at Cycle 26 |
-3.40
(24.29)
|
-9.38
(19.37)
|
| Nausea And Vomiting Scale: Change at Cycle 27 |
-5.04
(22.58)
|
-7.47
(20.70)
|
| Nausea And Vomiting Scale: Change at Cycle 28 |
-1.25
(20.11)
|
-6.41
(17.69)
|
| Nausea and Vomiting Scale: Change at PT Visit 1 |
4.68
(22.20)
|
4.13
(23.91)
|
| Nausea and Vomiting Scale: Change at PT Visit 2 |
4.29
(23.05)
|
2.73
(21.60)
|
| Pain Symptom Scale: Cycle 1 (Baseline) |
23.92
(25.92)
|
23.72
(24.82)
|
| Pain Symptom Scale: Change at Cycle 2 |
-6.80
(24.69)
|
-6.38
(23.58)
|
| Pain Symptom Scale: Change at Cycle 3 |
-9.89
(25.16)
|
-7.23
(25.78)
|
| Pain Symptom Scale: Change at Cycle 4 |
-10.26
(24.78)
|
-7.46
(26.06)
|
| Pain Symptom Scale: Change at Cycle 5 |
-8.86
(25.88)
|
-6.25
(25.42)
|
| Pain Symptom Scale: Change at Cycle 6 |
-8.95
(25.73)
|
-7.33
(24.85)
|
| Pain Symptom Scale: Change at Cycle 7 |
-10.95
(26.13)
|
-7.46
(24.79)
|
| Pain Symptom Scale: Change at Cycle 8 |
-9.97
(25.80)
|
-8.53
(22.86)
|
| Pain Symptom Scale: Change at Cycle 9 |
-9.29
(24.83)
|
-7.82
(22.98)
|
| Pain Symptom Scale: Change at Cycle 10 |
-9.41
(26.10)
|
-8.13
(22.75)
|
| Pain Symptom Scale: Change at Cycle 11 |
-10.33
(25.77)
|
-6.34
(22.97)
|
| Pain Symptom Scale: Change at Cycle 12 |
-10.27
(23.10)
|
-5.24
(25.29)
|
| Pain Symptom Scale: Change at Cycle 13 |
-10.28
(25.79)
|
-4.80
(20.27)
|
| Pain Symptom Scale: Change at Cycle 14 |
-10.49
(25.49)
|
-5.56
(23.37)
|
| Pain Symptom Scale: Change at Cycle 15 |
-11.15
(22.86)
|
-3.74
(22.77)
|
| Pain Symptom Scale: Change at Cycle 16 |
-9.91
(22.94)
|
-4.71
(23.66)
|
| Pain Symptom Scale: Change at Cycle 17 |
-7.59
(25.00)
|
-5.63
(22.63)
|
| Pain Symptom Scale: Change at Cycle 18 |
-8.82
(23.42)
|
-8.22
(20.68)
|
| Pain Symptom Scale: Change at Cycle 19 |
-8.16
(25.13)
|
-5.05
(21.48)
|
| Pain Symptom Scale: Change at Cycle 20 |
-6.94
(25.90)
|
-6.08
(19.24)
|
| Pain Symptom Scale: Change at Cycle 21 |
-9.92
(27.15)
|
-6.48
(23.44)
|
| Pain Symptom Scale: Change at Cycle 22 |
-7.71
(26.96)
|
-8.51
(19.62)
|
| Pain Symptom Scale: Change at Cycle 23 |
-10.85
(22.03)
|
-7.95
(26.29)
|
| Pain Symptom Scale: Change at Cycle 24 |
-10.00
(24.39)
|
-10.00
(17.21)
|
| Pain Symptom Scale: Change at Cycle 25 |
-9.94
(24.09)
|
-12.96
(19.96)
|
| Pain Symptom Scale: Change at Cycle 26 |
-10.54
(22.49)
|
-8.33
(18.45)
|
| Pain Symptom Scale: Change at Cycle 27 |
-11.24
(22.34)
|
-5.75
(21.95)
|
| Pain Symptom Scale: Change at Cycle 28 |
-10.42
(27.91)
|
-9.62
(19.54)
|
| Pain Symptom Scale: Change at PT Visit 1 |
1.13
(27.27)
|
2.06
(28.70)
|
| Pain Symptom Scale: Change at PT Visit 2 |
-1.49
(28.39)
|
5.45
(29.96)
|
| Physical Functional Scale: Cycle 1 (Baseline) |
80.86
(19.53)
|
82.05
(18.32)
|
| Physical Functional Scale: Change at Cycle 2 |
-3.58
(14.56)
|
-3.01
(15.34)
|
| Physical Functional Scale: Change at Cycle 3 |
-2.99
(17.19)
|
-3.92
(17.03)
|
| Physical Functional Scale: Change at Cycle 4 |
-3.28
(18.87)
|
-3.50
(17.99)
|
| Physical Functional Scale: Change at Cycle 5 |
-3.10
(19.35)
|
-4.62
(17.62)
|
| Physical Functional Scale: Change at Cycle 6 |
-5.00
(20.30)
|
-3.84
(18.65)
|
| Physical Functional Scale: Change at Cycle 7 |
-3.66
(20.75)
|
-3.79
(19.82)
|
| Physical Functional Scale: Change at Cycle 8 |
-2.24
(21.14)
|
-1.56
(18.55)
|
| Physical Functional Scale: Change at Cycle 9 |
-1.59
(20.21)
|
-0.75
(18.44)
|
| Physical Functional Scale: Change at Cycle 10 |
0.11
(19.93)
|
-0.27
(17.16)
|
| Physical Functional Scale: Change at Cycle 11 |
0.35
(19.43)
|
0.27
(17.09)
|
| Physical Functional Scale: Change at Cycle 12 |
-1.05
(20.06)
|
0.89
(16.35)
|
| Physical Functional Scale: Change at Cycle 13 |
-0.80
(20.65)
|
0.27
(17.41)
|
| Physical Functional Scale: Change at Cycle 14 |
-0.02
(20.14)
|
1.70
(18.09)
|
| Physical Functional Scale: Change at Cycle 15 |
0.41
(18.91)
|
-0.95
(17.99)
|
| Physical Functional Scale: Change at Cycle 16 |
-1.08
(19.85)
|
-0.08
(18.18)
|
| Physical Functional Scale: Change at Cycle 17 |
-0.46
(19.43)
|
-0.81
(17.55)
|
| Physical Functional Scale: Change at Cycle 18 |
0.13
(19.74)
|
0.75
(16.85)
|
| Physical Functional Scale: Change at Cycle 19 |
1.39
(19.82)
|
1.31
(14.38)
|
| Physical Functional Scale: Change at Cycle 20 |
0.71
(21.08)
|
0.85
(16.74)
|
| Physical Functional Scale: Change at Cycle 21 |
0.42
(22.20)
|
0.25
(18.18)
|
| Physical Functional Scale: Change at Cycle 22 |
-2.79
(21.90)
|
1.42
(16.79)
|
| Physical Functional Scale: Change at Cycle 23 |
-1.48
(21.47)
|
0.61
(19.60)
|
| Physical Functional Scale: Change at Cycle 24 |
-2.67
(22.27)
|
3.00
(16.47)
|
| Physical Functional Scale: Change at Cycle 25 |
-2.18
(20.61)
|
4.81
(15.91)
|
| Physical Functional Scale: Change at Cycle 26 |
-1.90
(20.09)
|
-1.88
(20.69)
|
| Physical Functional Scale: Change at Cycle 27 |
0.16
(18.66)
|
-3.68
(19.40)
|
| Physical Functional Scale: Change at Cycle 28 |
-1.17
(17.79)
|
-2.82
(18.97)
|
| Physical Functional Scale: Change at PT Visit 1 |
-11.37
(23.67)
|
-7.51
(20.53)
|
| Physical Functional Scale: Change at PT Visit 2 |
-11.49
(24.31)
|
-11.82
(20.27)
|
| Global Health Status Scale: Cycle 1 (Baseline) |
59.77
(22.88)
|
59.90
(22.11)
|
| Global Health Status Scale: Change at Cycle 2 |
1.81
(23.35)
|
4.29
(23.42)
|
| Global Health Status Scale: Change at Cycle 3 |
1.56
(25.05)
|
2.86
(25.03)
|
| Global Health Status Scale: Change at Cycle 4 |
1.39
(25.26)
|
4.15
(23.79)
|
| Global Health Status Scale: Change at Cycle 5 |
1.17
(25.70)
|
3.92
(23.05)
|
| Global Health Status Scale: Change at Cycle 6 |
0.68
(27.89)
|
3.61
(23.13)
|
| Global Health Status Scale: Change at Cycle 7 |
1.83
(27.81)
|
3.33
(22.77)
|
| Global Health Status Scale: Change at Cycle 8 |
3.06
(27.09)
|
5.18
(23.18)
|
| Global Health Status Scale: Change at Cycle 9 |
4.39
(26.25)
|
4.68
(22.99)
|
| Global Health Status Scale: Change at Cycle 10 |
4.80
(25.35)
|
5.07
(22.77)
|
| Global Health Status Scale: Change at Cycle 11 |
5.78
(26.62)
|
3.82
(23.75)
|
| Global Health Status Scale: Change at Cycle 12 |
3.11
(24.89)
|
5.34
(24.47)
|
| Global Health Status Scale: Change at Cycle 13 |
3.51
(23.82)
|
3.83
(23.78)
|
| Global Health Status Scale: Change at Cycle 14 |
5.97
(23.09)
|
4.82
(24.86)
|
| Global Health Status Scale: Change at Cycle 15 |
4.26
(25.98)
|
1.70
(24.46)
|
| Global Health Status Scale: Change at Cycle 16 |
3.12
(25.16)
|
3.04
(23.77)
|
| Global Health Status Scale: Change at Cycle 17 |
2.93
(24.84)
|
3.83
(24.84)
|
| Global Health Status Scale: Change at Cycle 18 |
3.02
(23.88)
|
2.58
(27.08)
|
| Global Health Status Scale: Change at Cycle 19 |
3.25
(26.39)
|
3.97
(25.43)
|
| Global Health Status Scale: Change at Cycle 20 |
5.12
(24.20)
|
4.89
(25.69)
|
| Global Health Status Scale: Change at Cycle 21 |
5.38
(23.87)
|
5.40
(24.72)
|
| Global Health Status Scale: Change at Cycle 22 |
3.79
(22.56)
|
3.19
(25.57)
|
| Global Health Status Scale: Change at Cycle 23 |
4.03
(23.85)
|
4.07
(27.18)
|
| Global Health Status Scale: Change at Cycle 24 |
4.24
(22.66)
|
2.92
(30.58)
|
| Global Health Status Scale: Change at Cycle 25 |
3.59
(22.38)
|
8.10
(25.39)
|
| Global Health Status Scale: Change at Cycle 26 |
7.27
(24.55)
|
5.47
(26.91)
|
| Global Health Status Scale: Change at Cycle 27 |
7.54
(23.19)
|
1.72
(28.38)
|
| Global Health Status Scale: Change at Cycle 28 |
4.49
(22.69)
|
4.81
(28.98)
|
| Global Health Status Scale: Change at PT Visit 1 |
-7.24
(27.24)
|
-6.14
(24.97)
|
| Global Health Status Scale: Change at PT Visit 2 |
-2.72
(27.46)
|
-5.68
(26.57)
|
| Role Functional Scale: Cycle 1 (Baseline) |
77.06
(27.02)
|
79.33
(25.12)
|
| Role Functional Scale: Change at Cycle 2 |
-3.78
(24.99)
|
-2.82
(24.35)
|
| Role Functional Scale: Change at Cycle 3 |
-3.62
(25.96)
|
-4.55
(28.00)
|
| Role Functional Scale: Change at Cycle 4 |
-4.64
(27.69)
|
-5.99
(26.87)
|
| Role Functional Scale: Change at Cycle 5 |
-4.72
(27.68)
|
-7.41
(27.25)
|
| Role Functional Scale: Change at Cycle 6 |
-6.13
(28.94)
|
-6.03
(28.51)
|
| Role Functional Scale: Change at Cycle 7 |
-4.82
(29.75)
|
-5.34
(26.31)
|
| Role Functional Scale: Change at Cycle 8 |
-1.85
(28.87)
|
-2.38
(26.41)
|
| Role Functional Scale: Change at Cycle 9 |
-1.19
(28.57)
|
-2.47
(27.29)
|
| Role Functional Scale: Change at Cycle 10 |
-1.79
(28.10)
|
0.90
(25.97)
|
| Role Functional Scale: Change at Cycle 11 |
-0.78
(28.34)
|
-2.69
(24.94)
|
| Role Functional Scale: Change at Cycle 12 |
-1.05
(27.28)
|
0.24
(24.07)
|
| Role Functional Scale: Change at Cycle 13 |
-2.01
(26.61)
|
-2.40
(24.91)
|
| Role Functional Scale: Change at Cycle 14 |
-0.86
(27.27)
|
-1.31
(25.66)
|
| Role Functional Scale: Change at Cycle 15 |
-1.03
(27.51)
|
-3.23
(25.40)
|
| Role Functional Scale: Change at Cycle 16 |
-3.16
(28.73)
|
-2.35
(25.48)
|
| Role Functional Scale: Change at Cycle 17 |
-1.04
(26.69)
|
-3.38
(25.88)
|
| Role Functional Scale: Change at Cycle 18 |
-0.16
(27.10)
|
0.23
(26.05)
|
| Role Functional Scale: Change at Cycle 19 |
1.04
(27.55)
|
-0.25
(23.48)
|
| Role Functional Scale: Change at Cycle 20 |
-1.19
(30.04)
|
0.79
(23.46)
|
| Role Functional Scale: Change at Cycle 21 |
-0.84
(28.98)
|
0.00
(27.47)
|
| Role Functional Scale: Change at Cycle 22 |
-2.24
(27.96)
|
1.06
(22.63)
|
| Role Functional Scale: Change at Cycle 23 |
-3.44
(30.11)
|
1.14
(25.01)
|
| Role Functional Scale: Change at Cycle 24 |
-4.44
(29.73)
|
2.08
(24.22)
|
| Role Functional Scale: Change at Cycle 25 |
-3.53
(29.21)
|
4.63
(26.91)
|
| Role Functional Scale: Change at Cycle 26 |
-1.36
(28.02)
|
0.52
(26.60)
|
| Role Functional Scale: Change at Cycle 27 |
-1.55
(30.82)
|
-4.02
(29.77)
|
| Role Functional Scale: Change at Cycle 28 |
-0.42
(27.86)
|
-3.85
(29.56)
|
| Role Functional Scale: Change at PT Visit 1 |
-14.61
(30.41)
|
-9.49
(28.64)
|
| Role Functional Scale: Change at PT Visit 2 |
-10.73
(31.94)
|
-15.45
(31.82)
|
| Social Functional Scale: Cycle 1 (Baseline) |
77.96
(24.09)
|
75.90
(24.69)
|
| Social Functional Scale: Change at Cycle 2 |
-3.45
(24.07)
|
-0.44
(23.09)
|
| Social Functional Scale: Change at Cycle 3 |
-4.62
(25.25)
|
-2.07
(25.35)
|
| Social Functional Scale: Change at Cycle 4 |
-2.59
(25.08)
|
-1.70
(26.58)
|
| Social Functional Scale: Change at Cycle 5 |
-5.54
(27.03)
|
-3.26
(27.24)
|
| Social Functional Scale: Change at Cycle 6 |
-5.72
(27.87)
|
-1.04
(27.20)
|
| Social Functional Scale: Change at Cycle 7 |
-2.69
(27.13)
|
-0.15
(26.00)
|
| Social Functional Scale: Change at Cycle 8 |
-1.72
(26.93)
|
1.08
(26.49)
|
| Social Functional Scale: Change at Cycle 9 |
0.56
(27.59)
|
0.77
(25.11)
|
| Social Functional Scale: Change at Cycle 10 |
-0.81
(27.31)
|
2.31
(25.75)
|
| Social Functional Scale: Change at Cycle 11 |
0.58
(27.35)
|
1.94
(24.39)
|
| Social Functional Scale: Change at Cycle 12 |
0.52
(28.59)
|
2.40
(24.70)
|
| Social Functional Scale: Change at Cycle 13 |
0.83
(25.31)
|
2.10
(25.73)
|
| Social Functional Scale: Change at Cycle 14 |
1.98
(26.71)
|
2.12
(24.89)
|
| Social Functional Scale: Change at Cycle 15 |
1.79
(27.24)
|
0.00
(27.08)
|
| Social Functional Scale: Change at Cycle 16 |
-0.72
(25.76)
|
0.39
(25.84)
|
| Social Functional Scale: Change at Cycle 17 |
-0.45
(26.51)
|
1.58
(24.39)
|
| Social Functional Scale: Change at Cycle 18 |
-0.98
(25.99)
|
2.11
(26.42)
|
| Social Functional Scale: Change at Cycle 19 |
2.26
(26.56)
|
3.28
(21.53)
|
| Social Functional Scale: Change at Cycle 20 |
1.59
(27.09)
|
0.79
(22.88)
|
| Social Functional Scale: Change at Cycle 21 |
1.27
(28.09)
|
5.86
(22.00)
|
| Social Functional Scale: Change at Cycle 22 |
1.24
(27.72)
|
2.84
(24.16)
|
| Social Functional Scale: Change at Cycle 23 |
6.08
(27.32)
|
1.89
(22.51)
|
| Social Functional Scale: Change at Cycle 24 |
5.83
(25.64)
|
4.17
(24.39)
|
| Social Functional Scale: Change at Cycle 25 |
1.60
(27.27)
|
2.78
(23.40)
|
| Social Functional Scale: Change at Cycle 26 |
3.74
(26.19)
|
1.56
(24.45)
|
| Social Functional Scale: Change at Cycle 27 |
5.81
(24.37)
|
-1.72
(26.85)
|
| Social Functional Scale: Change at Cycle 28 |
6.25
(23.48)
|
-0.64
(24.26)
|
| Social Functional Scale: Change at PT Visit 1 |
-9.13
(26.47)
|
-3.80
(28.74)
|
| Social Functional Scale: Change at PT Visit 2 |
-5.45
(28.49)
|
-8.48
(28.98)
|
| Insomnia Symptom Scale: Cycle 1 (Baseline) |
22.94
(28.00)
|
25.41
(28.81)
|
| Insomnia Symptom Scale: Change at Cycle 2 |
-0.69
(26.82)
|
-0.39
(28.27)
|
| Insomnia Symptom Scale: Change at Cycle 3 |
-3.53
(27.03)
|
-3.48
(30.14)
|
| Insomnia Symptom Scale: Change at Cycle 4 |
-2.88
(28.14)
|
-3.62
(30.40)
|
| Insomnia Symptom Scale: Change at Cycle 5 |
-2.21
(29.27)
|
-2.66
(30.17)
|
| Insomnia Symptom Scale: Change at Cycle 6 |
-2.94
(28.63)
|
-5.58
(32.53)
|
| Insomnia Symptom Scale: Change at Cycle 7 |
-4.56
(28.42)
|
-4.82
(32.98)
|
| Insomnia Symptom Scale: Change at Cycle 8 |
-6.13
(27.72)
|
-6.45
(30.75)
|
| Insomnia Symptom Scale: Change at Cycle 9 |
-8.97
(25.69)
|
-6.12
(30.32)
|
| Insomnia Symptom Scale: Change at Cycle 10 |
-8.24
(26.69)
|
-4.42
(28.79)
|
| Insomnia Symptom Scale: Change at Cycle 11 |
-8.97
(28.19)
|
-5.81
(27.69)
|
| Insomnia Symptom Scale: Change at Cycle 12 |
-8.81
(27.67)
|
-6.43
(26.49)
|
| Insomnia Symptom Scale: Change at Cycle 13 |
-10.17
(26.71)
|
-5.11
(24.29)
|
| Insomnia Symptom Scale: Change at Cycle 14 |
-9.14
(26.84)
|
-7.84
(24.45)
|
| Insomnia Symptom Scale: Change at Cycle 15 |
-9.74
(28.89)
|
-5.10
(21.59)
|
| Insomnia Symptom Scale: Change at Cycle 16 |
-8.91
(26.14)
|
-4.31
(26.62)
|
| Insomnia Symptom Scale: Change at Cycle 17 |
-11.01
(26.62)
|
-5.41
(26.48)
|
| Insomnia Symptom Scale: Change at Cycle 18 |
-8.82
(28.12)
|
-8.45
(20.09)
|
| Insomnia Symptom Scale: Change at Cycle 19 |
-11.46
(29.35)
|
-7.58
(22.49)
|
| Insomnia Symptom Scale: Change at Cycle 20 |
-10.32
(27.37)
|
-5.29
(25.55)
|
| Insomnia Symptom Scale: Change at Cycle 21 |
-11.81
(27.24)
|
-4.94
(27.02)
|
| Insomnia Symptom Scale: Change at Cycle 22 |
-10.95
(31.46)
|
-7.80
(19.92)
|
| Insomnia Symptom Scale: Change at Cycle 23 |
-10.58
(34.82)
|
-6.06
(23.04)
|
| Insomnia Symptom Scale: Change at Cycle 24 |
-9.44
(31.94)
|
-7.50
(21.99)
|
| Insomnia Symptom Scale: Change at Cycle 25 |
-10.26
(28.42)
|
-8.33
(26.87)
|
| Insomnia Symptom Scale: Change at Cycle 26 |
-9.52
(32.63)
|
-4.17
(20.30)
|
| Insomnia Symptom Scale: Change at Cycle 27 |
-13.18
(30.11)
|
-4.60
(19.36)
|
| Insomnia Symptom Scale: Change at Cycle 28 |
-11.67
(31.62)
|
-1.28
(22.07)
|
| Insomnia Symptom Scale: Change at PT Visit 1 |
2.81
(29.19)
|
-1.32
(30.81)
|
| Insomnia Symptom Scale: Change at PT Visit 2 |
5.67
(29.23)
|
3.03
(31.13)
|
| Title | Change From Baseline in EORTC QLQ-Gastric Cancer Module (EORTC QLQ-STO22) Score |
|---|---|
| Description | The EORTC QLQ-STO22 is a gastric cancer quality of life questionnaire. There are 22 questions concerning disease, treatment related symptoms, side effects, dysphagia, nutritional aspects, and questions about the emotional problems of gastric cancer (dysphagia, pain, reflux, eating restrictions, anxiety, dry mouth, body image, and hair loss). The questions are grouped into five scales and 4 single items which are related to the symptoms of the disease. Most questions used 4-point scale (1 'Not at all' to 4 'Very much'; 1 question was a yes or no answer). A linear transformation was used to standardize all scores and single-items to a scale of 0 to 100; higher score=better level of functioning or greater degree of symptoms. A positive value means an increase, while a negative values means a decrease, in score at the indicated time-point relative to the score at baseline (Cycle 1, Day 1). |
| Time Frame | Day 1 of each 21-day treatment cycle up to 28 and 60-90 days (post-treatment [PT] monitoring visits 1 and 2, respectively) after Day 1 of last treatment cycle (up to approximately 3.5 years) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the ITT population (includes all randomized participants, regardless of whether study medication was received) with both a baseline assessment and at least 1 post-treatment assessment are included in the analysis. |
| Arm/Group Title | Pertuzumab + Trastuzumab + Chemotherapy | Placebo + Trastuzumab + Chemotherapy |
|---|---|---|
| Arm/Group Description | Participants received pertuzumab in combination with trastuzumab and chemotherapy (cisplatin and fluoropyrimidine [capecitabine or 5-fluorouracil]) for the first 6 treatment cycles (cycle length = 21 days). Thereafter, participants continued to receive pertuzumab and trastuzumab until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason. | Participants received placebo in combination with trastuzumab and chemotherapy (cisplatin and fluoropyrimidine [capecitabine or 5-fluorouracil]) for the first 6 treatment cycles (cycle length = 21 days). Thereafter, participants continued to receive placebo and trastuzumab until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason. |
| Measure Participants | 388 | 392 |
| Anxiety: Cycle 1 (Baseline) |
40.10
(25.85)
|
40.48
(25.32)
|
| Anxiety: Change at Cycle 2 |
-2.58
(21.72)
|
-4.11
(21.19)
|
| Anxiety: Change at Cycle 3 |
-4.14
(22.45)
|
-3.87
(23.19)
|
| Anxiety: Change at Cycle 4 |
-4.52
(23.01)
|
-7.25
(23.16)
|
| Anxiety: Change at Cycle 5 |
-4.10
(22.94)
|
-7.39
(24.36)
|
| Anxiety: Change at Cycle 6 |
-4.54
(23.97)
|
-8.42
(25.21)
|
| Anxiety: Change at Cycle 7 |
-6.40
(24.00)
|
-10.40
(24.37)
|
| Anxiety: Change at Cycle 8 |
-9.00
(23.17)
|
-11.92
(24.50)
|
| Anxiety: Change at Cycle 9 |
-10.09
(23.30)
|
-11.43
(23.24)
|
| Anxiety: Change at Cycle 10 |
-11.17
(25.05)
|
-12.64
(22.09)
|
| Anxiety: Change at Cycle 11 |
-10.78
(23.47)
|
-12.09
(21.84)
|
| Anxiety: Change at Cycle 12 |
-12.62
(26.24)
|
-13.16
(23.11)
|
| Anxiety: Change at Cycle 13 |
-13.32
(25.93)
|
-13.33
(22.47)
|
| Anxiety: Change at Cycle 14 |
-14.32
(26.49)
|
-12.43
(23.59)
|
| Anxiety: Change at Cycle 15 |
-13.42
(26.64)
|
-10.65
(25.74)
|
| Anxiety: Change at Cycle 16 |
-12.75
(26.87)
|
-12.57
(23.89)
|
| Anxiety: Change at Cycle 17 |
-13.41
(27.30)
|
-12.79
(21.01)
|
| Anxiety: Change at Cycle 18 |
-13.53
(28.05)
|
-12.38
(22.90)
|
| Anxiety: Change at Cycle 19 |
-14.50
(27.41)
|
-12.48
(20.08)
|
| Anxiety: Change at Cycle 20 |
-15.34
(29.21)
|
-12.37
(23.73)
|
| Anxiety: Change at Cycle 21 |
-16.03
(28.84)
|
-14.47
(25.00)
|
| Anxiety: Change at Cycle 22 |
-13.30
(30.77)
|
-15.46
(23.83)
|
| Anxiety: Change at Cycle 23 |
-17.28
(30.64)
|
-14.47
(29.55)
|
| Anxiety: Change at Cycle 24 |
-16.11
(30.65)
|
-17.09
(23.76)
|
| Anxiety: Change at Cycle 25 |
-16.03
(29.47)
|
-17.78
(23.68)
|
| Anxiety: Change at Cycle 26 |
-19.73
(30.28)
|
-13.26
(22.11)
|
| Anxiety: Change at Cycle 27 |
-21.71
(29.89)
|
-12.70
(20.67)
|
| Anxiety: Change at Cycle 28 |
-22.51
(29.34)
|
-12.89
(22.38)
|
| Anxiety: Change at PT Visit 1 |
-0.73
(25.18)
|
-4.73
(27.21)
|
| Anxiety: Change at PT Visit 2 |
-4.04
(28.24)
|
-3.98
(25.02)
|
| Body Image: Cycle 1 (Baseline) |
23.53
(28.40)
|
23.68
(27.47)
|
| Body Image: Change at Cycle 2 |
1.33
(28.19)
|
1.20
(26.44)
|
| Body Image: Change at Cycle 3 |
1.48
(29.06)
|
3.88
(28.03)
|
| Body Image: Change at Cycle 4 |
4.20
(28.51)
|
1.15
(27.19)
|
| Body Image: Change at Cycle 5 |
2.86
(30.91)
|
1.06
(25.74)
|
| Body Image: Change at Cycle 6 |
0.75
(30.11)
|
2.78
(28.48)
|
| Body Image: Change at Cycle 7 |
-0.56
(28.94)
|
0.29
(25.53)
|
| Body Image: Change at Cycle 8 |
-1.74
(29.83)
|
0.00
(26.30)
|
| Body Image: Change at Cycle 9 |
-3.58
(28.74)
|
-0.69
(24.52)
|
| Body Image: Change at Cycle 10 |
-5.07
(30.15)
|
-3.25
(24.55)
|
| Body Image: Change at Cycle 11 |
-4.62
(30.24)
|
-1.53
(25.46)
|
| Body Image: Change at Cycle 12 |
-5.31
(31.92)
|
-2.66
(27.04)
|
| Body Image: Change at Cycle 13 |
-4.73
(30.23)
|
-2.73
(25.99)
|
| Body Image: Change at Cycle 14 |
-5.43
(29.70)
|
-4.62
(24.05)
|
| Body Image: Change at Cycle 15 |
-3.08
(30.63)
|
-2.43
(27.03)
|
| Body Image: Change at Cycle 16 |
-1.74
(32.99)
|
-1.19
(26.10)
|
| Body Image: Change at Cycle 17 |
-2.70
(32.76)
|
-2.28
(21.75)
|
| Body Image: Change at Cycle 18 |
-2.64
(30.44)
|
-5.71
(23.38)
|
| Body Image: Change at Cycle 19 |
-2.81
(33.57)
|
-5.21
(20.76)
|
| Body Image: Change at Cycle 20 |
-3.97
(30.79)
|
-5.38
(22.74)
|
| Body Image: Change at Cycle 21 |
1.69
(30.15)
|
-8.18
(26.07)
|
| Body Image: Change at Cycle 22 |
-1.49
(32.01)
|
-10.87
(22.28)
|
| Body Image: Change at Cycle 23 |
-5.82
(24.35)
|
-8.53
(29.18)
|
| Body Image: Change at Cycle 24 |
-0.56
(31.25)
|
-11.11
(23.36)
|
| Body Image: Change at Cycle 25 |
-3.21
(28.97)
|
-11.43
(24.18)
|
| Body Image: Change at Cycle 26 |
-4.76
(29.66)
|
-6.45
(18.09)
|
| Body Image: Change at Cycle 27 |
0.78
(24.65)
|
-7.14
(21.00)
|
| Body Image: Change at Cycle 28 |
-4.27
(26.69)
|
-4.00
(24.19)
|
| Body Image: Change at PT Visit 1 |
2.48
(31.57)
|
3.42
(29.31)
|
| Body Image: Change at PT Visit 2 |
2.36
(35.40)
|
6.35
(27.38)
|
| Dry Mouth: Cycle 1 (Baseline) |
21.80
(25.07)
|
23.32
(26.79)
|
| Dry Mouth: Change at Cycle 2 |
7.72
(28.70)
|
3.00
(25.43)
|
| Dry Mouth: Change at Cycle 3 |
6.10
(28.65)
|
4.87
(27.33)
|
| Dry Mouth: Change at Cycle 4 |
4.76
(29.40)
|
2.66
(31.06)
|
| Dry Mouth: Change at Cycle 5 |
2.47
(29.67)
|
2.57
(28.68)
|
| Dry Mouth: Change at Cycle 6 |
2.96
(30.14)
|
1.19
(27.65)
|
| Dry Mouth: Change at Cycle 7 |
-1.96
(28.82)
|
0.44
(28.54)
|
| Dry Mouth: Change at Cycle 8 |
-2.43
(28.68)
|
-2.66
(26.27)
|
| Dry Mouth: Change at Cycle 9 |
-3.70
(25.70)
|
-4.32
(24.74)
|
| Dry Mouth: Change at Cycle 10 |
-6.27
(25.04)
|
-3.46
(23.53)
|
| Dry Mouth: Change at Cycle 11 |
-7.69
(25.46)
|
-1.96
(26.56)
|
| Dry Mouth: Change at Cycle 12 |
-8.18
(24.22)
|
-4.35
(26.36)
|
| Dry Mouth: Change at Cycle 13 |
-9.69
(24.08)
|
-8.48
(26.50)
|
| Dry Mouth: Change at Cycle 14 |
-8.33
(24.60)
|
-3.63
(29.78)
|
| Dry Mouth: Change at Cycle 15 |
-7.89
(22.20)
|
-7.29
(26.58)
|
| Dry Mouth: Change at Cycle 16 |
-6.32
(24.44)
|
-8.33
(27.80)
|
| Dry Mouth: Change at Cycle 17 |
-7.44
(23.12)
|
-3.20
(24.32)
|
| Dry Mouth: Change at Cycle 18 |
-5.56
(24.86)
|
-8.10
(28.62)
|
| Dry Mouth: Change at Cycle 19 |
-5.90
(24.18)
|
-7.69
(25.53)
|
| Dry Mouth: Change at Cycle 20 |
-6.35
(26.62)
|
-9.68
(27.25)
|
| Dry Mouth: Change at Cycle 21 |
-7.17
(24.27)
|
-9.43
(20.02)
|
| Dry Mouth: Change at Cycle 22 |
-3.98
(26.29)
|
-8.70
(23.76)
|
| Dry Mouth: Change at Cycle 23 |
-7.94
(23.73)
|
-3.88
(25.42)
|
| Dry Mouth: Change at Cycle 24 |
-6.67
(25.15)
|
-9.40
(28.56)
|
| Dry Mouth: Change at Cycle 25 |
-8.33
(22.75)
|
-9.52
(28.66)
|
| Dry Mouth: Change at Cycle 26 |
-2.72
(23.41)
|
-7.53
(26.82)
|
| Dry Mouth: Change at Cycle 27 |
-6.98
(21.28)
|
-7.14
(27.75)
|
| Dry Mouth: Change at Cycle 28 |
-8.55
(21.24)
|
-8.00
(22.11)
|
| Dry Mouth: Change at PT Visit 1 |
0.19
(28.70)
|
2.38
(31.58)
|
| Dry Mouth: Change at PT Visit 2 |
-1.35
(30.09)
|
1.89
(25.95)
|
| Dysphagia: Cycle 1 (Baseline) |
16.29
(21.46)
|
14.15
(18.93)
|
| Dysphagia: Change at Cycle 2 |
-2.27
(17.64)
|
-0.53
(19.32)
|
| Dysphagia: Change at Cycle 3 |
-3.39
(18.57)
|
-2.15
(19.67)
|
| Dysphagia: Change at Cycle 4 |
-2.94
(18.93)
|
-1.08
(18.79)
|
| Dysphagia: Change at Cycle 5 |
-3.22
(19.92)
|
-1.83
(18.99)
|
| Dysphagia: Change at Cycle 6 |
-4.20
(18.99)
|
-2.25
(18.70)
|
| Dysphagia: Change at Cycle 7 |
-4.83
(20.56)
|
-1.97
(19.94)
|
| Dysphagia: Change at Cycle 8 |
-5.96
(18.80)
|
-3.29
(18.48)
|
| Dysphagia: Change at Cycle 9 |
-6.17
(18.21)
|
-3.86
(18.49)
|
| Dysphagia: Change at Cycle 10 |
-6.03
(17.37)
|
-4.61
(16.87)
|
| Dysphagia: Change at Cycle 11 |
-6.25
(17.09)
|
-2.83
(17.03)
|
| Dysphagia: Change at Cycle 12 |
-7.06
(17.65)
|
-4.19
(15.84)
|
| Dysphagia: Change at Cycle 13 |
-6.93
(18.71)
|
-3.54
(17.61)
|
| Dysphagia: Change at Cycle 14 |
-8.01
(18.53)
|
-4.95
(18.22)
|
| Dysphagia: Change at Cycle 15 |
-6.45
(17.38)
|
-2.14
(18.69)
|
| Dysphagia: Change at Cycle 16 |
-4.41
(18.29)
|
-3.70
(21.08)
|
| Dysphagia: Change at Cycle 17 |
-5.36
(16.87)
|
-3.20
(14.99)
|
| Dysphagia: Change at Cycle 18 |
-4.90
(16.44)
|
-3.33
(19.78)
|
| Dysphagia: Change at Cycle 19 |
-4.40
(17.10)
|
-3.59
(14.31)
|
| Dysphagia: Change at Cycle 20 |
-2.51
(16.21)
|
-3.76
(15.83)
|
| Dysphagia: Change at Cycle 21 |
-3.80
(19.24)
|
-2.10
(17.84)
|
| Dysphagia: Change at Cycle 22 |
-3.65
(20.41)
|
-4.83
(15.65)
|
| Dysphagia: Change at Cycle 23 |
-4.23
(18.87)
|
-3.88
(17.63)
|
| Dysphagia: Change at Cycle 24 |
-5.00
(18.35)
|
-3.70
(13.08)
|
| Dysphagia: Change at Cycle 25 |
-5.98
(19.61)
|
-2.22
(16.79)
|
| Dysphagia: Change at Cycle 26 |
-5.67
(20.43)
|
-2.87
(16.22)
|
| Dysphagia: Change at Cycle 27 |
-5.68
(20.91)
|
-4.37
(12.22)
|
| Dysphagia: Change at Cycle 28 |
-8.26
(19.86)
|
-3.56
(11.44)
|
| Dysphagia: Change at PT Visit 1 |
0.44
(24.15)
|
2.83
(22.63)
|
| Dysphagia: Change at PT Visit 2 |
-2.81
(24.40)
|
3.25
(19.81)
|
| Eating Restrictions: Cycle 1 (Baseline) |
23.26
(21.78)
|
22.33
(20.22)
|
| Eating Restrictions: Change at Cycle 2 |
-1.41
(19.36)
|
-1.54
(19.62)
|
| Eating Restrictions: Change at Cycle 3 |
-1.04
(21.09)
|
-2.20
(20.94)
|
| Eating Restrictions: Change at Cycle 4 |
-2.24
(20.81)
|
-1.39
(23.36)
|
| Eating Restrictions: Change at Cycle 5 |
-1.39
(22.10)
|
-0.09
(23.31)
|
| Eating Restrictions: Change at Cycle 6 |
-1.35
(22.77)
|
-3.32
(23.14)
|
| Eating Restrictions: Change at Cycle 7 |
-2.45
(22.68)
|
-2.67
(21.66)
|
| Eating Restrictions: Change at Cycle 8 |
-4.29
(22.70)
|
-5.56
(19.87)
|
| Eating Restrictions: Change at Cycle 9 |
-6.99
(21.16)
|
-6.48
(19.69)
|
| Eating Restrictions: Change at Cycle 10 |
-7.06
(21.32)
|
-5.89
(19.30)
|
| Eating Restrictions: Change at Cycle 11 |
-8.22
(21.25)
|
-5.05
(19.98)
|
| Eating Restrictions: Change at Cycle 12 |
-7.74
(21.16)
|
-6.34
(19.87)
|
| Eating Restrictions: Change at Cycle 13 |
-8.55
(20.41)
|
-8.41
(19.57)
|
| Eating Restrictions: Change at Cycle 14 |
-8.62
(19.16)
|
-8.58
(21.16)
|
| Eating Restrictions: Change at Cycle 15 |
-6.85
(20.92)
|
-5.56
(21.21)
|
| Eating Restrictions: Change at Cycle 16 |
-5.77
(22.01)
|
-6.94
(20.36)
|
| Eating Restrictions: Change at Cycle 17 |
-5.56
(21.95)
|
-7.42
(17.76)
|
| Eating Restrictions: Change at Cycle 18 |
-7.27
(20.40)
|
-6.90
(21.14)
|
| Eating Restrictions: Change at Cycle 19 |
-7.03
(21.78)
|
-5.38
(18.07)
|
| Eating Restrictions: Change at Cycle 20 |
-4.56
(21.03)
|
-4.44
(16.72)
|
| Eating Restrictions: Change at Cycle 21 |
-5.80
(22.58)
|
-5.03
(19.97)
|
| Eating Restrictions: Change at Cycle 22 |
-3.65
(21.79)
|
-6.16
(16.80)
|
| Eating Restrictions: Change at Cycle 23 |
-3.70
(22.74)
|
-5.23
(20.25)
|
| Eating Restrictions: Change at Cycle 24 |
-5.00
(20.77)
|
-7.91
(15.76)
|
| Eating Restrictions: Change at Cycle 25 |
-5.77
(21.10)
|
-5.95
(16.61)
|
| Eating Restrictions: Change at Cycle 26 |
-6.80
(21.22)
|
-2.42
(22.89)
|
| Eating Restrictions: Change at Cycle 27 |
-5.62
(23.48)
|
-3.87
(10.26)
|
| Eating Restrictions: Change at Cycle 28 |
-7.91
(21.79)
|
-5.00
(11.02)
|
| Eating Restrictions: Change at PT Visit 1 |
1.52
(24.48)
|
0.94
(24.70)
|
| Eating Restrictions: Change at PT Visit 2 |
-2.10
(25.32)
|
0.94
(21.46)
|
| Hair Loss: Cycle 1 (Baseline) |
4.73
(13.28)
|
4.04
(13.20)
|
| Hair Loss: Change at Cycle 2 |
0.20
(14.85)
|
1.27
(16.59)
|
| Hair Loss: Change at Cycle 3 |
4.34
(17.51)
|
4.52
(18.71)
|
| Hair Loss: Change at Cycle 4 |
5.40
(18.46)
|
6.53
(20.99)
|
| Hair Loss: Change at Cycle 5 |
6.12
(19.38)
|
7.18
(19.49)
|
| Hair Loss: Change at Cycle 6 |
6.93
(18.87)
|
10.07
(22.94)
|
| Hair Loss: Change at Cycle 7 |
5.72
(19.91)
|
9.26
(22.92)
|
| Hair Loss: Change at Cycle 8 |
5.00
(18.96)
|
7.38
(23.05)
|
| Hair Loss: Change at Cycle 9 |
2.38
(17.43)
|
6.46
(21.06)
|
| Hair Loss: Change at Cycle 10 |
0.64
(16.88)
|
4.22
(19.51)
|
| Hair Loss: Change at Cycle 11 |
-0.10
(17.02)
|
2.54
(17.51)
|
| Hair Loss: Change at Cycle 12 |
0.21
(19.70)
|
1.96
(15.72)
|
| Hair Loss: Change at Cycle 13 |
0.36
(18.91)
|
2.29
(15.46)
|
| Hair Loss: Change at Cycle 14 |
-1.37
(17.59)
|
1.83
(15.15)
|
| Hair Loss: Change at Cycle 15 |
-0.39
(15.65)
|
1.58
(12.65)
|
| Hair Loss: Change at Cycle 16 |
-1.47
(17.47)
|
1.42
(13.91)
|
| Hair Loss: Change at Cycle 17 |
-1.07
(17.75)
|
0.23
(12.57)
|
| Hair Loss: Change at Cycle 18 |
-1.68
(17.58)
|
-0.71
(13.14)
|
| Hair Loss: Change at Cycle 19 |
-0.90
(18.12)
|
0.51
(14.12)
|
| Hair Loss: Change at Cycle 20 |
-0.20
(19.21)
|
-1.61
(12.70)
|
| Hair Loss: Change at Cycle 21 |
-1.07
(19.43)
|
-1.57
(8.81)
|
| Hair Loss: Change at Cycle 22 |
-0.50
(16.66)
|
-3.26
(11.98)
|
| Hair Loss: Change at Cycle 23 |
-0.54
(16.79)
|
-1.19
(11.28)
|
| Hair Loss: Change at Cycle 24 |
-1.39
(17.44)
|
1.71
(16.13)
|
| Hair Loss: Change at Cycle 25 |
-1.96
(18.75)
|
-0.95
(9.85)
|
| Hair Loss: Change at Cycle 26 |
-1.02
(19.37)
|
-0.54
(10.08)
|
| Hair Loss: Change at Cycle 27 |
-3.10
(15.96)
|
-0.60
(10.62)
|
| Hair Loss: Change at Cycle 28 |
-4.70
(20.57)
|
-1.33
(10.67)
|
| Hair Loss: Change at PT Visit 1 |
4.98
(19.73)
|
4.51
(20.39)
|
| Hair Loss: Change at PT Visit 2 |
15.82
(25.35)
|
22.22
(30.81)
|
| Pain: Cycle 1 (Baseline) |
26.48
(21.34)
|
26.47
(20.70)
|
| Pain: Change at Cycle 2 |
-4.63
(20.30)
|
-5.86
(19.15)
|
| Pain: Change at Cycle 3 |
-6.96
(20.37)
|
-5.86
(20.68)
|
| Pain: Change at Cycle 4 |
-6.45
(21.47)
|
-7.48
(21.23)
|
| Pain: Change at Cycle 5 |
-7.28
(20.95)
|
-6.89
(22.10)
|
| Pain: Change at Cycle 6 |
-7.24
(20.84)
|
-7.22
(21.62)
|
| Pain: Change at Cycle 7 |
-9.52
(21.18)
|
-6.62
(21.63)
|
| Pain: Change at Cycle 8 |
-10.53
(21.62)
|
-8.16
(20.11)
|
| Pain: Change at Cycle 9 |
-10.08
(19.60)
|
-8.98
(20.29)
|
| Pain: Change at Cycle 10 |
-10.63
(19.23)
|
-8.59
(20.38)
|
| Pain: Change at Cycle 11 |
-11.65
(19.35)
|
-8.01
(18.97)
|
| Pain: Change at Cycle 12 |
-11.76
(19.87)
|
-7.19
(19.11)
|
| Pain: Change at Cycle 13 |
-11.92
(18.93)
|
-9.24
(19.79)
|
| Pain: Change at Cycle 14 |
-11.66
(19.51)
|
-9.82
(19.91)
|
| Pain: Change at Cycle 15 |
-11.15
(18.16)
|
-8.51
(20.94)
|
| Pain: Change at Cycle 16 |
-8.72
(18.02)
|
-10.52
(21.30)
|
| Pain: Change at Cycle 17 |
-8.88
(18.17)
|
-9.93
(17.27)
|
| Pain: Change at Cycle 18 |
-8.31
(18.33)
|
-11.19
(18.16)
|
| Pain: Change at Cycle 19 |
-6.63
(17.25)
|
-10.38
(14.51)
|
| Pain: Change at Cycle 20 |
-5.72
(19.98)
|
-10.35
(16.65)
|
| Pain: Change at Cycle 21 |
-8.19
(18.27)
|
-7.55
(16.77)
|
| Pain: Change at Cycle 22 |
-9.08
(18.10)
|
-9.42
(16.72)
|
| Pain: Change at Cycle 23 |
-9.66
(20.75)
|
-8.53
(19.96)
|
| Pain: Change at Cycle 24 |
-9.86
(21.56)
|
-8.76
(15.53)
|
| Pain: Change at Cycle 25 |
-10.58
(19.88)
|
-8.10
(18.69)
|
| Pain: Change at Cycle 26 |
-9.01
(17.99)
|
-9.41
(17.58)
|
| Pain: Change at Cycle 27 |
-12.02
(17.28)
|
-9.23
(14.58)
|
| Pain: Change at Cycle 28 |
-11.54
(18.20)
|
-7.33
(13.46)
|
| Pain: Change at PT Visit 1 |
-1.70
(23.07)
|
-2.99
(23.86)
|
| Pain: Change at PT Visit 2 |
-7.49
(24.09)
|
-0.03
(22.04)
|
| Reflux Symptoms: Cycle 1 (Baseline) |
16.68
(19.03)
|
17.34
(18.31)
|
| Reflux Symptoms: Change at Cycle 2 |
-0.13
(16.33)
|
-1.99
(18.03)
|
| Reflux Symptoms: Change at Cycle 3 |
-0.52
(18.95)
|
-2.28
(19.53)
|
| Reflux Symptoms: Change at Cycle 4 |
-0.98
(19.18)
|
-1.90
(19.93)
|
| Reflux Symptoms: Change at Cycle 5 |
-1.92
(18.98)
|
-1.72
(20.10)
|
| Reflux Symptoms: Change at Cycle 6 |
-2.90
(20.42)
|
-3.59
(19.04)
|
| Reflux Symptoms: Change at Cycle 7 |
-4.18
(18.36)
|
-3.20
(20.21)
|
| Reflux Symptoms: Change at Cycle 8 |
-4.96
(19.39)
|
-5.74
(19.53)
|
| Reflux Symptoms: Change at Cycle 9 |
-5.02
(18.97)
|
-5.18
(19.81)
|
| Reflux Symptoms: Change at Cycle 10 |
-6.12
(17.81)
|
-6.48
(18.55)
|
| Reflux Symptoms: Change at Cycle 11 |
-6.44
(18.74)
|
-6.03
(18.07)
|
| Reflux Symptoms: Change at Cycle 12 |
-4.82
(18.00)
|
-7.49
(16.99)
|
| Reflux Symptoms: Change at Cycle 13 |
-6.42
(17.09)
|
-6.77
(18.19)
|
| Reflux Symptoms: Change at Cycle 14 |
-5.39
(18.24)
|
-7.37
(17.45)
|
| Reflux Symptoms: Change at Cycle 15 |
-5.00
(16.66)
|
-4.98
(18.72)
|
| Reflux Symptoms: Change at Cycle 16 |
-3.07
(18.39)
|
-4.89
(22.31)
|
| Reflux Symptoms: Change at Cycle 17 |
-3.35
(18.38)
|
-4.57
(20.44)
|
| Reflux Symptoms: Change at Cycle 18 |
-2.94
(18.36)
|
-6.51
(20.33)
|
| Reflux Symptoms: Change at Cycle 19 |
-2.43
(16.38)
|
-6.15
(18.43)
|
| Reflux Symptoms: Change at Cycle 20 |
-1.85
(18.32)
|
-5.38
(18.63)
|
| Reflux Symptoms: Change at Cycle 21 |
-1.83
(18.44)
|
-4.19
(17.73)
|
| Reflux Symptoms: Change at Cycle 22 |
-3.81
(19.30)
|
-7.00
(19.65)
|
| Reflux Symptoms: Change at Cycle 23 |
-5.11
(17.03)
|
-6.98
(19.70)
|
| Reflux Symptoms: Change at Cycle 24 |
-4.07
(19.30)
|
-7.98
(18.19)
|
| Reflux Symptoms: Change at Cycle 25 |
-5.56
(18.86)
|
-5.71
(16.69)
|
| Reflux Symptoms: Change at Cycle 26 |
-4.99
(20.67)
|
-4.30
(21.98)
|
| Reflux Symptoms: Change at Cycle 27 |
-7.75
(20.51)
|
-6.75
(16.10)
|
| Reflux Symptoms: Change at Cycle 28 |
-7.12
(18.64)
|
-4.44
(11.56)
|
| Reflux Symptoms: Change at PT Visit 1 |
0.88
(20.01)
|
-0.45
(22.92)
|
| Reflux Symptoms: Change at PT Visit 2 |
0.56
(18.67)
|
-1.47
(22.28)
|
| Taste: Cycle 1 (Baseline) |
13.79
(23.99)
|
16.22
(25.49)
|
| Taste: Change at Cycle 2 |
12.09
(28.78)
|
6.61
(26.94)
|
| Taste: Change at Cycle 3 |
16.72
(32.11)
|
9.99
(30.16)
|
| Taste: Change at Cycle 4 |
18.43
(34.70)
|
11.07
(31.93)
|
| Taste: Change at Cycle 5 |
17.61
(32.93)
|
11.85
(30.25)
|
| Taste: Change at Cycle 6 |
17.97
(31.20)
|
11.82
(32.21)
|
| Taste: Change at Cycle 7 |
16.25
(33.51)
|
9.19
(31.09)
|
| Taste: Change at Cycle 8 |
11.64
(29.81)
|
3.29
(28.13)
|
| Taste: Change at Cycle 9 |
9.22
(28.25)
|
1.73
(26.30)
|
| Taste: Change at Cycle 10 |
7.93
(26.41)
|
1.63
(28.79)
|
| Taste: Change at Cycle 11 |
4.96
(26.72)
|
2.61
(26.91)
|
| Taste: Change at Cycle 12 |
5.27
(24.82)
|
0.24
(24.66)
|
| Taste: Change at Cycle 13 |
4.08
(25.53)
|
-0.91
(25.33)
|
| Taste: Change at Cycle 14 |
0.49
(25.66)
|
-5.28
(24.37)
|
| Taste: Change at Cycle 15 |
3.08
(24.36)
|
-1.04
(26.25)
|
| Taste: Change at Cycle 16 |
5.51
(27.90)
|
-3.57
(20.71)
|
| Taste: Change at Cycle 17 |
4.80
(24.96)
|
-3.65
(23.28)
|
| Taste: Change at Cycle 18 |
3.59
(23.87)
|
-4.29
(23.34)
|
| Taste: Change at Cycle 19 |
3.13
(25.17)
|
-4.62
(15.45)
|
| Taste: Change at Cycle 20 |
5.56
(27.78)
|
-3.76
(18.21)
|
| Taste: Change at Cycle 21 |
6.33
(27.26)
|
-5.03
(17.78)
|
| Taste: Change at Cycle 22 |
9.45
(30.04)
|
-4.35
(16.64)
|
| Taste: Change at Cycle 23 |
8.99
(30.06)
|
0.00
(23.00)
|
| Taste: Change at Cycle 24 |
7.78
(28.37)
|
-5.13
(19.55)
|
| Taste: Change at Cycle 25 |
3.21
(28.97)
|
-4.76
(18.33)
|
| Taste: Change at Cycle 26 |
4.08
(34.45)
|
-3.23
(21.70)
|
| Taste: Change at Cycle 27 |
4.65
(29.62)
|
-3.57
(20.96)
|
| Taste: Change at Cycle 28 |
3.42
(21.35)
|
-6.67
(25.46)
|
| Taste: Change at PT Visit 1 |
12.76
(34.59)
|
9.06
(33.56)
|
| Taste: Change at PT Visit 2 |
8.42
(31.35)
|
6.67
(28.64)
|
| Title | Maximum Serum Concentration (Cmax) of Pertuzumab |
|---|---|
| Description | |
| Time Frame | Post-dose (0.5 hour after end of 30-60 minutes infusion) on Day 1 of Cycles 1, 2, 4, and 8 (1 cycle = 21 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The pharmacokinetic analysis included all participants who were treated with study medication and who had at least one measurable concentration of pertuzumab or trastuzumab. In this analysis, results are reported only for evaluable participants who received pertuzumab. |
| Arm/Group Title | Pertuzumab + Trastuzumab + Chemotherapy |
|---|---|
| Arm/Group Description | Participants received pertuzumab in combination with trastuzumab and chemotherapy (cisplatin and fluoropyrimidine [capecitabine or 5-fluorouracil]) for the first 6 treatment cycles (cycle length = 21 days). Thereafter, participants continued to receive pertuzumab and trastuzumab until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason. |
| Measure Participants | 374 |
| Cycle 1 |
258
(90.3)
|
| Cycle 2 |
288
(83.7)
|
| Cycle 4 |
341
(111)
|
| Cycle 8 |
371
(127)
|
| Title | Cmax of Trastuzumab |
|---|---|
| Description | |
| Time Frame | Post-dose (0.5 hour after end of 30-60 minutes infusion) on Day 1 of Cycles 1, 2, 4, and 8 (1 cycle = 21 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The pharmacokinetic analysis included all participants who were treated with study medication and who had at least one measurable concentration of pertuzumab or trastuzumab. Data are reported for evaluable participants. |
| Arm/Group Title | Pertuzumab + Trastuzumab + Chemotherapy | Placebo + Trastuzumab + Chemotherapy |
|---|---|---|
| Arm/Group Description | Participants received pertuzumab in combination with trastuzumab and chemotherapy (cisplatin and fluoropyrimidine [capecitabine or 5-fluorouracil]) for the first 6 treatment cycles (cycle length = 21 days). Thereafter, participants continued to receive pertuzumab and trastuzumab until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason. | Participants received placebo in combination with trastuzumab and chemotherapy (cisplatin and fluoropyrimidine [capecitabine or 5-fluorouracil]) for the first 6 treatment cycles (cycle length = 21 days). Thereafter, participants continued to receive placebo and trastuzumab until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason. |
| Measure Participants | 372 | 375 |
| Cycle 1 |
142
(86.8)
|
139
(58.6)
|
| Cycle 2 |
120
(46.6)
|
120
(44.3)
|
| Cycle 4 |
127
(50.9)
|
129
(58.1)
|
| Cycle 8 |
130
(50.8)
|
147
(90.2)
|
| Title | Minimum Serum Concentration (Cmin) of Pertuzumab |
|---|---|
| Description | |
| Time Frame | Pre-dose (0-6 hours before infusion) on Day 1 of Cycles 1, 2, 3, 4, 6, and 8 (1 cycle = 21 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The pharmacokinetic analysis included all participants who were treated with study medication and who had at least one measurable concentration of pertuzumab or trastuzumab. In this analysis, results are reported only for evaluable participants who received pertuzumab. |
| Arm/Group Title | Pertuzumab + Trastuzumab + Chemotherapy |
|---|---|
| Arm/Group Description | Participants received pertuzumab in combination with trastuzumab and chemotherapy (cisplatin and fluoropyrimidine [capecitabine or 5-fluorouracil]) for the first 6 treatment cycles (cycle length = 21 days). Thereafter, participants continued to receive pertuzumab and trastuzumab until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason. |
| Measure Participants | 376 |
| Cycle 1 |
NA
(NA)
|
| Cycle 2 |
42.4
(24.8)
|
| Cycle 3 |
74.0
(40.9)
|
| Cycle 4 |
90.4
(42.4)
|
| Cycle 6 |
114
(51.8)
|
| Cycle 8 |
142
(67.9)
|
| Title | Cmin of Trastuzumab |
|---|---|
| Description | |
| Time Frame | Pre-dose (0-6 hours before infusion) on Day 1 of Cycles 1, 2, 3, 4, 6, and 8 (1 cycle = 21 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The pharmacokinetic analysis included all participants who were treated with study medication and who had at least one measurable concentration of pertuzumab or trastuzumab. Data are reported for evaluable participants. |
| Arm/Group Title | Pertuzumab + Trastuzumab + Chemotherapy | Placebo + Trastuzumab + Chemotherapy |
|---|---|---|
| Arm/Group Description | Participants received pertuzumab in combination with trastuzumab and chemotherapy (cisplatin and fluoropyrimidine [capecitabine or 5-fluorouracil]) for the first 6 treatment cycles (cycle length = 21 days). Thereafter, participants continued to receive pertuzumab and trastuzumab until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason. | Participants received placebo in combination with trastuzumab and chemotherapy (cisplatin and fluoropyrimidine [capecitabine or 5-fluorouracil]) for the first 6 treatment cycles (cycle length = 21 days). Thereafter, participants continued to receive placebo and trastuzumab until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason. |
| Measure Participants | 379 | 381 |
| Cycle 1 |
NA
(NA)
|
NA
(NA)
|
| Cycle 2 |
15.4
(11.3)
|
17.2
(15.4)
|
| Cycle 3 |
19.9
(13.4)
|
20.7
(15.2)
|
| Cycle 4 |
22.9
(12.7)
|
24.1
(19.0)
|
| Cycle 6 |
26.3
(14.8)
|
29.8
(21.9)
|
| Cycle 8 |
32.7
(15.0)
|
37.4
(20.3)
|
Adverse Events
| Time Frame | From Baseline until end of post-treatment follow-up (up to 70 months) | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | All adverse events (AEs) that occurred during the study and until the post-treatment safety follow-up visit approximately 28 days after last study medication were to be recorded. The safety population included all participants who received any amount of any study medication: those who received any amount of pertuzumab were included in the pertuzumab arm; all other treated participants were included in the placebo arm. | |||
| Arm/Group Title | Pertuzumab + Trastuzumab + Chemotherapy | Placebo + Trastuzumab + Chemotherapy | ||
| Arm/Group Description | Participants received pertuzumab in combination with trastuzumab and chemotherapy (cisplatin and fluoropyrimidine [capecitabine or 5-fluorouracil]) for the first 6 treatment cycles (cycle length = 21 days). Thereafter, participants continued to receive pertuzumab and trastuzumab until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason. | Participants received placebo in combination with trastuzumab and chemotherapy (cisplatin and fluoropyrimidine [capecitabine or 5-fluorouracil]) for the first 6 treatment cycles (cycle length = 21 days). Thereafter, participants continued to receive placebo and trastuzumab until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason. | ||
All Cause Mortality |
||||
| Pertuzumab + Trastuzumab + Chemotherapy | Placebo + Trastuzumab + Chemotherapy | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 299/385 (77.7%) | 318/388 (82%) | ||
Serious Adverse Events |
||||
| Pertuzumab + Trastuzumab + Chemotherapy | Placebo + Trastuzumab + Chemotherapy | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 178/385 (46.2%) | 156/388 (40.2%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 8/385 (2.1%) | 11 | 16/388 (4.1%) | 19 |
| Disseminated intravascular coagulation | 0/385 (0%) | 0 | 1/388 (0.3%) | 1 |
| Febrile neutropenia | 6/385 (1.6%) | 6 | 9/388 (2.3%) | 9 |
| Neutropenia | 3/385 (0.8%) | 4 | 3/388 (0.8%) | 3 |
| Pancytopenia | 0/385 (0%) | 0 | 3/388 (0.8%) | 3 |
| Thrombocytopenia | 2/385 (0.5%) | 2 | 1/388 (0.3%) | 1 |
| Cardiac disorders | ||||
| Acute myocardial infarction | 4/385 (1%) | 4 | 0/388 (0%) | 0 |
| Atrial fibrillation | 0/385 (0%) | 0 | 1/388 (0.3%) | 1 |
| Atrial septal defect acquired | 1/385 (0.3%) | 1 | 0/388 (0%) | 0 |
| Atrioventricular block complete | 0/385 (0%) | 0 | 1/388 (0.3%) | 1 |
| Cardiac arrest | 1/385 (0.3%) | 1 | 1/388 (0.3%) | 1 |
| Cardiac failure | 3/385 (0.8%) | 3 | 1/388 (0.3%) | 1 |
| Cardiac ventricular thrombosis | 1/385 (0.3%) | 1 | 0/388 (0%) | 0 |
| Intracardiac thrombus | 1/385 (0.3%) | 1 | 0/388 (0%) | 0 |
| Myocardial infarction | 2/385 (0.5%) | 2 | 1/388 (0.3%) | 1 |
| Myocarditis | 0/385 (0%) | 0 | 1/388 (0.3%) | 1 |
| Prinzmetal angina | 1/385 (0.3%) | 1 | 0/388 (0%) | 0 |
| Acute coronary syndrome | 1/385 (0.3%) | 1 | 0/388 (0%) | 0 |
| Ear and labyrinth disorders | ||||
| Tinnitus | 0/385 (0%) | 0 | 1/388 (0.3%) | 1 |
| Endocrine disorders | ||||
| Autoimmune thyroiditis | 1/385 (0.3%) | 1 | 0/388 (0%) | 0 |
| Inappropriate antidiuretic hormone secretion | 1/385 (0.3%) | 1 | 1/388 (0.3%) | 1 |
| Pseudoaldosteronism | 1/385 (0.3%) | 1 | 0/388 (0%) | 0 |
| Gastrointestinal disorders | ||||
| Abdominal pain | 3/385 (0.8%) | 3 | 2/388 (0.5%) | 2 |
| Abdominal pain upper | 0/385 (0%) | 0 | 1/388 (0.3%) | 1 |
| Colitis | 0/385 (0%) | 0 | 2/388 (0.5%) | 2 |
| Constipation | 0/385 (0%) | 0 | 1/388 (0.3%) | 1 |
| Diarrhoea | 17/385 (4.4%) | 20 | 20/388 (5.2%) | 22 |
| Duodenal stenosis | 1/385 (0.3%) | 1 | 0/388 (0%) | 0 |
| Dysphagia | 4/385 (1%) | 4 | 1/388 (0.3%) | 1 |
| Enteritis | 1/385 (0.3%) | 1 | 0/388 (0%) | 0 |
| Enterocolitis | 0/385 (0%) | 0 | 4/388 (1%) | 4 |
| Gastric haemorrhage | 6/385 (1.6%) | 7 | 2/388 (0.5%) | 2 |
| Gastric perforation | 2/385 (0.5%) | 2 | 2/388 (0.5%) | 2 |
| Gastric stenosis | 1/385 (0.3%) | 1 | 0/388 (0%) | 0 |
| Gastric ulcer | 1/385 (0.3%) | 1 | 1/388 (0.3%) | 1 |
| Gastrointestinal disorder | 0/385 (0%) | 0 | 1/388 (0.3%) | 1 |
| Gastrointestinal haemorrhage | 0/385 (0%) | 0 | 3/388 (0.8%) | 4 |
| Gastrointestinal inflammation | 1/385 (0.3%) | 1 | 1/388 (0.3%) | 1 |
| Gastrointestinal obstruction | 0/385 (0%) | 0 | 1/388 (0.3%) | 1 |
| Gastrointestinal perforation | 0/385 (0%) | 0 | 1/388 (0.3%) | 1 |
| Gastrointestinal ulcer | 0/385 (0%) | 0 | 1/388 (0.3%) | 1 |
| Gastrooesophageal reflux disease | 0/385 (0%) | 0 | 1/388 (0.3%) | 1 |
| Haematemesis | 0/385 (0%) | 0 | 1/388 (0.3%) | 1 |
| Haemorrhoids | 1/385 (0.3%) | 1 | 0/388 (0%) | 0 |
| Ileus | 2/385 (0.5%) | 2 | 1/388 (0.3%) | 2 |
| Ileus paralytic | 1/385 (0.3%) | 1 | 0/388 (0%) | 0 |
| Intestinal mass | 0/385 (0%) | 0 | 1/388 (0.3%) | 1 |
| Intestinal obstruction | 0/385 (0%) | 0 | 1/388 (0.3%) | 1 |
| Lower gastrointestinal haemorrhage | 0/385 (0%) | 0 | 2/388 (0.5%) | 2 |
| Melaena | 2/385 (0.5%) | 2 | 0/388 (0%) | 0 |
| Nausea | 7/385 (1.8%) | 7 | 7/388 (1.8%) | 9 |
| Obstruction gastric | 2/385 (0.5%) | 2 | 5/388 (1.3%) | 7 |
| Oesophageal haemorrhage | 1/385 (0.3%) | 1 | 1/388 (0.3%) | 1 |
| Stomatitis | 2/385 (0.5%) | 2 | 2/388 (0.5%) | 2 |
| Upper gastrointestinal haemorrhage | 3/385 (0.8%) | 3 | 5/388 (1.3%) | 5 |
| Vomiting | 7/385 (1.8%) | 8 | 13/388 (3.4%) | 17 |
| Gastric pneumatosis | 1/385 (0.3%) | 1 | 0/388 (0%) | 0 |
| Mechanical ileus | 0/385 (0%) | 0 | 1/388 (0.3%) | 1 |
| General disorders | ||||
| Asthenia | 5/385 (1.3%) | 8 | 1/388 (0.3%) | 1 |
| Chest pain | 0/385 (0%) | 0 | 1/388 (0.3%) | 1 |
| Death | 8/385 (2.1%) | 8 | 9/388 (2.3%) | 9 |
| Fatigue | 4/385 (1%) | 4 | 0/388 (0%) | 0 |
| General physical health deterioration | 1/385 (0.3%) | 1 | 0/388 (0%) | 0 |
| Hypothermia | 1/385 (0.3%) | 1 | 0/388 (0%) | 0 |
| Malaise | 0/385 (0%) | 0 | 1/388 (0.3%) | 1 |
| Mucosal inflammation | 4/385 (1%) | 4 | 3/388 (0.8%) | 3 |
| Multiple organ dysfunction syndrome | 0/385 (0%) | 0 | 2/388 (0.5%) | 2 |
| Non-cardiac chest pain | 0/385 (0%) | 0 | 1/388 (0.3%) | 1 |
| Pyrexia | 2/385 (0.5%) | 2 | 1/388 (0.3%) | 1 |
| Hepatobiliary disorders | ||||
| Cholecystitis | 1/385 (0.3%) | 1 | 0/388 (0%) | 0 |
| Cholecystitis acute | 1/385 (0.3%) | 1 | 3/388 (0.8%) | 4 |
| Hepatic function abnormal | 0/385 (0%) | 0 | 1/388 (0.3%) | 1 |
| Immune system disorders | ||||
| Cytokine release syndrome | 1/385 (0.3%) | 1 | 0/388 (0%) | 0 |
| Hypersensitivity | 1/385 (0.3%) | 1 | 0/388 (0%) | 0 |
| Infections and infestations | ||||
| Abdominal infection | 0/385 (0%) | 0 | 1/388 (0.3%) | 1 |
| Arthritis bacterial | 1/385 (0.3%) | 1 | 0/388 (0%) | 0 |
| Bacteraemia | 2/385 (0.5%) | 2 | 1/388 (0.3%) | 1 |
| Biliary sepsis | 0/385 (0%) | 0 | 1/388 (0.3%) | 1 |
| Bronchitis | 1/385 (0.3%) | 1 | 0/388 (0%) | 0 |
| Cellulitis | 1/385 (0.3%) | 1 | 0/388 (0%) | 0 |
| Device related infection | 2/385 (0.5%) | 2 | 0/388 (0%) | 0 |
| Device related sepsis | 1/385 (0.3%) | 1 | 0/388 (0%) | 0 |
| Diarrhoea infectious | 1/385 (0.3%) | 1 | 0/388 (0%) | 0 |
| Gastroenteritis | 0/385 (0%) | 0 | 2/388 (0.5%) | 2 |
| Hepatitis B | 0/385 (0%) | 0 | 1/388 (0.3%) | 1 |
| Infection | 0/385 (0%) | 0 | 3/388 (0.8%) | 3 |
| Liver abscess | 1/385 (0.3%) | 1 | 2/388 (0.5%) | 2 |
| Parotitis | 0/385 (0%) | 0 | 1/388 (0.3%) | 1 |
| Peritonitis | 1/385 (0.3%) | 1 | 0/388 (0%) | 0 |
| Pneumonia | 14/385 (3.6%) | 15 | 14/388 (3.6%) | 14 |
| Pneumonia Klebsiella | 0/385 (0%) | 0 | 1/388 (0.3%) | 1 |
| Respiratory tract infection | 0/385 (0%) | 0 | 1/388 (0.3%) | 1 |
| Sepsis | 8/385 (2.1%) | 8 | 2/388 (0.5%) | 2 |
| Septic shock | 3/385 (0.8%) | 3 | 4/388 (1%) | 4 |
| Upper respiratory tract infection | 3/385 (0.8%) | 3 | 2/388 (0.5%) | 2 |
| Urinary tract infection | 1/385 (0.3%) | 1 | 0/388 (0%) | 0 |
| Urosepsis | 0/385 (0%) | 0 | 1/388 (0.3%) | 1 |
| Appendicitis | 1/385 (0.3%) | 1 | 0/388 (0%) | 0 |
| Vascular device infection | 1/385 (0.3%) | 1 | 0/388 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||
| Anastomotic stenosis | 1/385 (0.3%) | 1 | 0/388 (0%) | 0 |
| Craniocerebral injury | 1/385 (0.3%) | 1 | 0/388 (0%) | 0 |
| Fall | 2/385 (0.5%) | 2 | 1/388 (0.3%) | 1 |
| Femoral neck fracture | 0/385 (0%) | 0 | 1/388 (0.3%) | 1 |
| Fracture | 2/385 (0.5%) | 2 | 0/388 (0%) | 0 |
| Gastrointestinal anastomotic leak | 0/385 (0%) | 0 | 1/388 (0.3%) | 1 |
| Head injury | 1/385 (0.3%) | 1 | 0/388 (0%) | 0 |
| Hip fracture | 0/385 (0%) | 0 | 1/388 (0.3%) | 1 |
| Infusion related reaction | 3/385 (0.8%) | 3 | 2/388 (0.5%) | 2 |
| Injury | 1/385 (0.3%) | 1 | 0/388 (0%) | 0 |
| Limb injury | 1/385 (0.3%) | 1 | 0/388 (0%) | 0 |
| Spinal compression fracture | 1/385 (0.3%) | 1 | 0/388 (0%) | 0 |
| Ankle fracture | 1/385 (0.3%) | 1 | 0/388 (0%) | 0 |
| Thermal burn | 1/385 (0.3%) | 1 | 0/388 (0%) | 0 |
| Investigations | ||||
| Alanine aminotransferase increased | 0/385 (0%) | 0 | 1/388 (0.3%) | 1 |
| Aspartate aminotransferase increased | 0/385 (0%) | 0 | 1/388 (0.3%) | 1 |
| Blood bilirubin increased | 1/385 (0.3%) | 1 | 0/388 (0%) | 0 |
| Blood creatine phosphokinase increased | 1/385 (0.3%) | 1 | 0/388 (0%) | 0 |
| Blood creatinine increased | 1/385 (0.3%) | 1 | 2/388 (0.5%) | 2 |
| Creatinine renal clearance decreased | 1/385 (0.3%) | 1 | 0/388 (0%) | 0 |
| Weight decreased | 1/385 (0.3%) | 1 | 0/388 (0%) | 0 |
| Biopsy bone marrow | 0/385 (0%) | 0 | 1/388 (0.3%) | 1 |
| Metabolism and nutrition disorders | ||||
| Cachexia | 1/385 (0.3%) | 2 | 0/388 (0%) | 0 |
| Decreased appetite | 17/385 (4.4%) | 18 | 9/388 (2.3%) | 9 |
| Dehydration | 9/385 (2.3%) | 10 | 9/388 (2.3%) | 9 |
| Diabetes mellitus | 0/385 (0%) | 0 | 1/388 (0.3%) | 1 |
| Diabetes mellitus inadequate control | 0/385 (0%) | 0 | 1/388 (0.3%) | 1 |
| Failure to thrive | 0/385 (0%) | 0 | 1/388 (0.3%) | 1 |
| Hyperglycaemia | 0/385 (0%) | 0 | 1/388 (0.3%) | 1 |
| Hypernatraemia | 1/385 (0.3%) | 1 | 0/388 (0%) | 0 |
| Hypocalcaemia | 2/385 (0.5%) | 2 | 1/388 (0.3%) | 1 |
| Hypokalaemia | 7/385 (1.8%) | 8 | 1/388 (0.3%) | 1 |
| Hypomagnesaemia | 2/385 (0.5%) | 2 | 2/388 (0.5%) | 2 |
| Hyponatraemia | 2/385 (0.5%) | 2 | 2/388 (0.5%) | 2 |
| Malnutrition | 1/385 (0.3%) | 1 | 1/388 (0.3%) | 2 |
| Musculoskeletal and connective tissue disorders | ||||
| Back pain | 0/385 (0%) | 0 | 1/388 (0.3%) | 1 |
| Gouty arthritis | 0/385 (0%) | 0 | 1/388 (0.3%) | 1 |
| Muscular weakness | 1/385 (0.3%) | 1 | 0/388 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Myelodysplastic syndrome | 1/385 (0.3%) | 1 | 1/388 (0.3%) | 1 |
| Rectosigmoid cancer stage 0 | 1/385 (0.3%) | 1 | 0/388 (0%) | 0 |
| Second primary malignancy | 0/385 (0%) | 0 | 1/388 (0.3%) | 1 |
| Tumour haemorrhage | 4/385 (1%) | 4 | 1/388 (0.3%) | 1 |
| Plasma cell myeloma | 0/385 (0%) | 0 | 1/388 (0.3%) | 1 |
| Nervous system disorders | ||||
| Anticholinergic syndrome | 1/385 (0.3%) | 1 | 0/388 (0%) | 0 |
| Cerebral haemorrhage | 0/385 (0%) | 0 | 1/388 (0.3%) | 1 |
| Cerebral infarction | 0/385 (0%) | 0 | 2/388 (0.5%) | 2 |
| Cerebral ischaemia | 1/385 (0.3%) | 1 | 0/388 (0%) | 0 |
| Cerebrovascular accident | 0/385 (0%) | 0 | 3/388 (0.8%) | 3 |
| Dizziness | 1/385 (0.3%) | 1 | 0/388 (0%) | 0 |
| Hydrocephalus | 0/385 (0%) | 0 | 1/388 (0.3%) | 1 |
| Ischaemic cerebral infarction | 0/385 (0%) | 0 | 1/388 (0.3%) | 1 |
| Ischaemic stroke | 1/385 (0.3%) | 1 | 1/388 (0.3%) | 1 |
| Loss of consciousness | 1/385 (0.3%) | 2 | 0/388 (0%) | 0 |
| Neuropathy peripheral | 1/385 (0.3%) | 1 | 0/388 (0%) | 0 |
| Presyncope | 1/385 (0.3%) | 1 | 0/388 (0%) | 0 |
| Seizure | 1/385 (0.3%) | 1 | 0/388 (0%) | 0 |
| Syncope | 2/385 (0.5%) | 2 | 0/388 (0%) | 0 |
| Subarachnoid haemorrhage | 0/385 (0%) | 0 | 1/388 (0.3%) | 1 |
| Epilepsy | 0/385 (0%) | 0 | 1/388 (0.3%) | 1 |
| Product Issues | ||||
| Device dislocation | 0/385 (0%) | 0 | 2/388 (0.5%) | 2 |
| Device occlusion | 1/385 (0.3%) | 1 | 0/388 (0%) | 0 |
| Psychiatric disorders | ||||
| Delirium | 1/385 (0.3%) | 2 | 0/388 (0%) | 0 |
| Depression | 0/385 (0%) | 0 | 1/388 (0.3%) | 1 |
| Suicide attempt | 0/385 (0%) | 0 | 1/388 (0.3%) | 1 |
| Renal and urinary disorders | ||||
| Acute kidney injury | 7/385 (1.8%) | 7 | 4/388 (1%) | 4 |
| Hydronephrosis | 0/385 (0%) | 0 | 1/388 (0.3%) | 1 |
| Renal failure | 2/385 (0.5%) | 2 | 3/388 (0.8%) | 3 |
| Renal impairment | 1/385 (0.3%) | 1 | 2/388 (0.5%) | 2 |
| Reproductive system and breast disorders | ||||
| Benign prostatic hyperplasia | 1/385 (0.3%) | 1 | 0/388 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Acute respiratory distress syndrome | 0/385 (0%) | 0 | 2/388 (0.5%) | 2 |
| Bronchospasm | 1/385 (0.3%) | 1 | 0/388 (0%) | 0 |
| Dyspnoea | 2/385 (0.5%) | 2 | 1/388 (0.3%) | 1 |
| Epistaxis | 1/385 (0.3%) | 1 | 0/388 (0%) | 0 |
| Hypoxia | 0/385 (0%) | 0 | 1/388 (0.3%) | 1 |
| Pneumothorax | 0/385 (0%) | 0 | 1/388 (0.3%) | 1 |
| Pulmonary embolism | 6/385 (1.6%) | 6 | 2/388 (0.5%) | 2 |
| Respiratory failure | 0/385 (0%) | 0 | 2/388 (0.5%) | 2 |
| Skin and subcutaneous tissue disorders | ||||
| Actinic keratosis | 1/385 (0.3%) | 1 | 0/388 (0%) | 0 |
| Vascular disorders | ||||
| Aortic aneurysm | 0/385 (0%) | 0 | 1/388 (0.3%) | 1 |
| Deep vein thrombosis | 3/385 (0.8%) | 3 | 0/388 (0%) | 0 |
| Embolism | 2/385 (0.5%) | 2 | 1/388 (0.3%) | 1 |
| Haemodynamic instability | 0/385 (0%) | 0 | 1/388 (0.3%) | 1 |
| Hypertensive crisis | 1/385 (0.3%) | 1 | 0/388 (0%) | 0 |
| Hypotension | 0/385 (0%) | 0 | 1/388 (0.3%) | 1 |
| Hypovolaemic shock | 0/385 (0%) | 0 | 1/388 (0.3%) | 1 |
| Iliac artery occlusion | 0/385 (0%) | 0 | 1/388 (0.3%) | 1 |
| Orthostatic hypotension | 1/385 (0.3%) | 1 | 0/388 (0%) | 0 |
| Peripheral ischaemia | 1/385 (0.3%) | 1 | 0/388 (0%) | 0 |
| Subclavian vein thrombosis | 0/385 (0%) | 0 | 1/388 (0.3%) | 1 |
| Thrombosis | 1/385 (0.3%) | 1 | 0/388 (0%) | 0 |
| Varicose vein | 1/385 (0.3%) | 1 | 0/388 (0%) | 0 |
| Venous thrombosis limb | 1/385 (0.3%) | 1 | 0/388 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||
| Pertuzumab + Trastuzumab + Chemotherapy | Placebo + Trastuzumab + Chemotherapy | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 373/385 (96.9%) | 376/388 (96.9%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 159/385 (41.3%) | 208 | 142/388 (36.6%) | 189 |
| Leukopenia | 80/385 (20.8%) | 148 | 69/388 (17.8%) | 113 |
| Neutropenia | 200/385 (51.9%) | 340 | 202/388 (52.1%) | 298 |
| Thrombocytopenia | 61/385 (15.8%) | 105 | 73/388 (18.8%) | 100 |
| Gastrointestinal disorders | ||||
| Abdominal distension | 25/385 (6.5%) | 36 | 19/388 (4.9%) | 24 |
| Abdominal pain | 44/385 (11.4%) | 60 | 51/388 (13.1%) | 59 |
| Abdominal pain upper | 28/385 (7.3%) | 33 | 23/388 (5.9%) | 25 |
| Constipation | 56/385 (14.5%) | 64 | 84/388 (21.6%) | 107 |
| Diarrhoea | 230/385 (59.7%) | 351 | 125/388 (32.2%) | 173 |
| Dyspepsia | 24/385 (6.2%) | 27 | 30/388 (7.7%) | 40 |
| Dysphagia | 28/385 (7.3%) | 34 | 32/388 (8.2%) | 38 |
| Nausea | 224/385 (58.2%) | 314 | 218/388 (56.2%) | 311 |
| Stomatitis | 81/385 (21%) | 102 | 69/388 (17.8%) | 86 |
| Vomiting | 147/385 (38.2%) | 200 | 122/388 (31.4%) | 167 |
| General disorders | ||||
| Asthenia | 59/385 (15.3%) | 83 | 60/388 (15.5%) | 78 |
| Chills | 37/385 (9.6%) | 37 | 17/388 (4.4%) | 19 |
| Fatigue | 144/385 (37.4%) | 182 | 123/388 (31.7%) | 166 |
| Mucosal inflammation | 43/385 (11.2%) | 60 | 34/388 (8.8%) | 40 |
| Oedema | 20/385 (5.2%) | 33 | 19/388 (4.9%) | 32 |
| Oedema peripheral | 27/385 (7%) | 31 | 33/388 (8.5%) | 36 |
| Pyrexia | 55/385 (14.3%) | 81 | 60/388 (15.5%) | 69 |
| Infections and infestations | ||||
| Upper respiratory tract infection | 24/385 (6.2%) | 37 | 13/388 (3.4%) | 18 |
| Nasopharyngitis | 21/385 (5.5%) | 22 | 18/388 (4.6%) | 24 |
| Injury, poisoning and procedural complications | ||||
| Infusion related reaction | 46/385 (11.9%) | 52 | 23/388 (5.9%) | 26 |
| Investigations | ||||
| Blood creatinine increased | 29/385 (7.5%) | 36 | 22/388 (5.7%) | 31 |
| Creatinine renal clearance decreased | 71/385 (18.4%) | 97 | 50/388 (12.9%) | 65 |
| Weight decreased | 78/385 (20.3%) | 80 | 49/388 (12.6%) | 51 |
| Ejection fraction decreased | 20/385 (5.2%) | 24 | 18/388 (4.6%) | 20 |
| Metabolism and nutrition disorders | ||||
| Decreased appetite | 172/385 (44.7%) | 243 | 158/388 (40.7%) | 218 |
| Hypoalbuminaemia | 20/385 (5.2%) | 24 | 21/388 (5.4%) | 23 |
| Hypocalcaemia | 24/385 (6.2%) | 32 | 23/388 (5.9%) | 26 |
| Hypokalaemia | 74/385 (19.2%) | 98 | 46/388 (11.9%) | 57 |
| Hypomagnesaemia | 30/385 (7.8%) | 38 | 21/388 (5.4%) | 22 |
| Hyponatraemia | 17/385 (4.4%) | 19 | 29/388 (7.5%) | 29 |
| Nervous system disorders | ||||
| Dizziness | 31/385 (8.1%) | 35 | 30/388 (7.7%) | 38 |
| Dysgeusia | 31/385 (8.1%) | 40 | 27/388 (7%) | 27 |
| Neuropathy peripheral | 34/385 (8.8%) | 38 | 29/388 (7.5%) | 30 |
| Peripheral sensory neuropathy | 29/385 (7.5%) | 37 | 34/388 (8.8%) | 35 |
| Psychiatric disorders | ||||
| Insomnia | 34/385 (8.8%) | 45 | 46/388 (11.9%) | 48 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Cough | 25/385 (6.5%) | 30 | 21/388 (5.4%) | 32 |
| Dyspnoea | 22/385 (5.7%) | 25 | 14/388 (3.6%) | 18 |
| Hiccups | 33/385 (8.6%) | 37 | 37/388 (9.5%) | 45 |
| Skin and subcutaneous tissue disorders | ||||
| Alopecia | 21/385 (5.5%) | 25 | 25/388 (6.4%) | 26 |
| Dry skin | 32/385 (8.3%) | 39 | 18/388 (4.6%) | 21 |
| Palmar-plantar erythrodysaesthesia syndrome | 86/385 (22.3%) | 91 | 100/388 (25.8%) | 112 |
| Pruritus | 38/385 (9.9%) | 51 | 16/388 (4.1%) | 25 |
| Rash | 27/385 (7%) | 30 | 13/388 (3.4%) | 15 |
| Skin hyperpigmentation | 17/385 (4.4%) | 17 | 21/388 (5.4%) | 21 |
| Vascular disorders | ||||
| Hypertension | 20/385 (5.2%) | 24 | 21/388 (5.4%) | 21 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The study being conducted under this agreement is part of the overall study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the study, but only after the first publication or presentation that involves the overall study. The Sponsor may request that confidential information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Results Point of Contact
| Name/Title | Medical Communications |
|---|---|
| Organization | Hoffmann-La Roche |
| Phone | 800-821-8590 |
| genentech@druginfo.com |
Responsible Party:
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01774786
Other Study ID Numbers:
- BO25114
- 2012-003554-83
First Posted:
Jan 24, 2013
Last Update Posted:
Dec 30, 2020
Last Verified:
Dec 1, 2020