A Study Of PF-05280014 [Trastuzumab-Pfizer] Or Herceptin® [Trastuzumab-EU] Plus Paclitaxel In HER2 Positive First Line Metastatic Breast Cancer Treatment (REFLECTIONS B327-02)

• Sponsor: Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01989676
• Collaborator: (none)
• Enrollment: 707
• Locations: 188
• Arms: 2
• Actual Duration (Months): 76.1
• Patients Per Site: 3.8
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The current study will compare the efficacy, safety, pharmacokinetics and immunogenicity of PF-05280014 in combination with paclitaxel versus trastuzumab sourced from the European Union (trastuzumab-EU) with paclitaxel in female patients with HER2-positive, metastatic breast cancer in the first-line treatment setting. The hypothesis to be tested in this study is that the efficacy (ORR) of PF-05280014 is similar to trastuzumab-EU.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Breast Cancer	Biological: PF-05280014; Drug: Paclitaxel; Biological: Herceptin®; Drug: Paclitaxel	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 707 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A PHASE 3 RANDOMIZED, DOUBLE-BLIND STUDY OF PF-05280014 PLUS PACLITAXEL VERSUS TRASTUZUMAB PLUS PACLITAXEL FOR THE FIRST-LINE TREATMENT OF PATIENTS WITH HER2-POSITIVE METASTATIC BREAST CANCER
• Actual Study Start Date: Feb 24, 2014
• Actual Primary Completion Date: Aug 24, 2016
• Actual Study Completion Date: Jun 27, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: PF-05280014	Biological: PF-05280014; Concentrate for solution for infusion, sterile vial 150 mg. Initial dose of 4 mg/kg over 90 minutes (depending on tolerability) IV infusion, then 2 mg/kg over 30 to 90 minutes (depending on tolerability) IV infusion until disease progression. Following completion of the paclitaxel administration period and beginning no earlier than Week 33 of the study, the PF-05280014 regimen may be changed at the discretion of the investigator to every 3 weeks at a dose of 6 mg/kg infused over 30 to 90 minutes depending on tolerability.; Other Names: Trastuzumab-Pfizer ; Drug: Paclitaxel; A nonaqueous solution intended for dilution with a suitable parenteral fluid prior to intravenous infusion. Paclitaxel is available in 30 mg (5 mL), 100 mg (16.7 mL), and 300 mg (50 mL) multidose vials. Each mL of sterile nonpyrogenic solution contains 6 mg paclitaxel. The starting dose of paclitaxel will be 80 mg/m^2 by IV infusion over 60 minutes (duration of infusion may be modified according to local standard of care, if applicable). Provision is made for dose reduction to 70 mg/m^2 and then 60 mg/m^2 as needed. In the absence of disease progression in the judgment of the investigator or prohibitive toxicity, patients will receive treatment with paclitaxel for at least 6 cycles or until maximal benefit of response is obtained, in the judgment of the investigator.
Active Comparator: Herceptin®	Biological: Herceptin®; Concentrate for solution for infusion, sterile vial 150 mg. Initial dose of 4 mg/kg over 90 minutes (depending on tolerability) IV infusion, then 2 mg/kg over 30 to 90 minutes (depending on tolerability) IV infusion weekly until disease progression. Following completion of the paclitaxel administration period and beginning no earlier than Week 33 of the study, the Herceptin® regimen may be changed at the discretion of the investigator to every 3 weeks at a dose of 6 mg/kg infused over 30 to 90 minutes depending on tolerability.; Other Names: Trastuzumab (EU) ; Drug: Paclitaxel; A nonaqueous solution intended for dilution with a suitable parenteral fluid prior to intravenous infusion. Paclitaxel is available in 30 mg (5 mL), 100 mg (16.7 mL), and 300 mg (50 mL) multidose vials. Each mL of sterile nonpyrogenic solution contains 6 mg paclitaxel. The starting dose of paclitaxel will be 80 mg/m^2 by IV infusion over 60 minutes (duration of infusion may be modified according to local standard of care, if applicable). Provision is made for dose reduction to 70 mg/m^2 and then 60 mg/m^2 as needed. In the absence of disease progression in the judgment of the investigator or prohibitive toxicity, patients will receive treatment with paclitaxel for at least 6 cycles or until maximal benefit of response is obtained, in the judgment of the investigator.

Outcome Measures

Primary Outcome Measures

1. Objective Response Rate (ORR) Derived From Central Radiology Assessments: ITT Population [From the date of randomization until all participants had either completed the Week 33 tumor assessment or discontinued study drug earlier than the Week 33 visit]

   ORR was defined as the percentage of participants who achieved complete response (CR, complete disappearance of all target lesions with the exception of nodal disease; all target nodes must have decreased to normal size [short axis <10 mm]) or partial response (PR, >=30% decrease from baseline of the sum of diameters (SOD) of all target measurable lesions; the short diameter was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions) by Week 25 of the study and confirmed on a follow-up assessment (Week 33+/-14 days), based on the assessments of the central radiology review in accordance with RECIST 1.1.

Secondary Outcome Measures

1. One-year Progression-Free Survival (PFS) Rate Derived From Central Radiology Assessments: ITT Population [From the date of randomization until 378 days post-randomization]

   One-year PFS rate was analyzed based on the time from date of randomization to first documentation of progressive disease (PD), or death due to any cause in the absence of documented PD, based on the assessments of the central radiology review in accordance with RECIST 1.1. PD was defined for target disease as at least a 20% increase in sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum was observed during therapy) with a minimum absolute increase of 5 mm. For non-target disease: PD was defined as unequivocal progression of pre-existing lesions and if overall tumor burden increased sufficiently to merit discontinuation of therapy; appearance of any new unequivocal malignant lesion was also considered PD. The 95% CI for the median time to event was based on the Brookmeyer and Crowley method.

2. Duration of Response (DOR) Per Central Radiology Assessments: ITT Population [From the date of randomization until 378 days post-randomization]

   DOR:time from first documentation of objective response (CR or PR) to first documentation of PD/death due to any cause in absence of documented PD, based on central radiology review. As per RECIST v1.1, CR:complete disappearance of all target lesions with exception of nodal disease; all target nodes reduced in short axis <10 mm. PR: >=30% decrease from baseline of SOD of target lesions; short diameter used in sum for target nodes,longest diameter used in sum for other target lesions. PD for target disease:at least 20% increase in SOD of target lesions above smallest sum observed (over baseline if no decrease in sum observed) with minimum absolute increase of 5 mm. For non-target disease:unequivocal progression of pre-existing lesions and if overall tumor burden increased sufficiently to merit discontinuation of therapy; appearance of any new unequivocal malignant lesion was also considered PD. The 95% CI for median time to event was based on the Brookmeyer and Crowley method.

3. Overall Survival: ITT Population [From the date of randomization until end of study (approximately 6 years)]

   Overall survival was analyzed based on the time from date of randomization to the date of death due to any cause. Participants last known to be alive were censored on the date of last contact. The 95% CI for the median time to event was based on the Brookmeyer and Crowley Method.

4. Serum Peak Concentration of PF-05280014 at Selected Cycles: Pharmacokinetics (PK) Population [1 hour post end of infusion on Day 1 of Cycles 1 and 5]

   Human PK serum samples were analyzed for concentrations of PF-05280014 using a validated, sensitive, and specific enzyme-linked immunosorbent assay (ELISA).

5. Serum Peak Concentration of Trastuzumab-EU at Selected Cycles: PK Population [1 hour post end of infusion on Day 1 of Cycles 1 and 5]

   Human PK serum samples were analyzed for concentrations of trastuzumab-EU using a validated, sensitive, and specific ELISA.

6. Serum Trough (Pre-dose) Concentration of PF-05280014 at Selected Cycles: PK Population [Pre-dose on Day 1 of Cycles 1, 3, 4, 5, 7, 8, 11, 14, 17 and Day 8 of Cycles 1 and 5]

   Human PK serum samples were analyzed for concentrations of PF-05280014 using a validated, sensitive, and specific ELISA.

7. Serum Trough (Pre-dose) Concentration of Trastuzumab-EU at Selected Cycles: PK Population [Pre-dose on Day 1 of Cycles 1, 3, 4, 5, 7, 8, 11, 14, 17 and Day 8 of Cycles 1 and 5]

   Human PK serum samples were analyzed for concentrations of trastuzumab-EU using a validated, sensitive, and specific ELISA.

8. Number of Participants With Positive Anti-Drug Antibodies (ADA) Sample: Safety Population [Pre-dose on Day 1 of Cycles 1, 3, 5, 8, 11, 14, 17]

   Two sensitive, specific, and semi-quantitative electrochemiluminescent (ECL) immunoassays, 1 for detecting antibodies against PF-05280014 and the other for detecting antibodies against trastuzumab, were used to analyze ADA samples. Serum samples were first screened for ADA. Any samples that were positive in the screening assay were further analyzed to confirm the positive result and determine the antibody titers. All samples were taken prior to dosing. The number of participants with a positive sample (titer >=1.0) is provided.

9. Number of Participants With Positive Neutralizing Antibodies (Nab) Prior to Treatment: Safety Population [Cycle 1 Day 1 (prior to treatment)]

   Human serum samples testing positive for the presence of ADA (anti-PF-05280014 or anti-trastuzumab-EU) were analyzed for the presence or absence of NAb (neutralizing anti-PF-05280014 or neutralizing anti-trastuzumab-EU antibodies) following a tiered approach using screening and titer determination. The number of participants at baseline (prior to treatment) with a positive NAb sample (titer >=1.48) is provided.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Histologically confirmed diagnosis of breast cancer.

• Presence of metastatic disease.

• Documentation of HER2 gene amplification or overexpression.

• Available tumor tissue for central review of HER2 status.

• At least 1 measurable lesion as defined by RECIST 1.1.

• Eastern Cooperative Oncology Group status of 0 to 2.

• Left ventricular ejection fraction within institutional range of normal, measured by either two dimensional echocardiogram or multigated acquisition scan.

Exclusion Criteria:

• Relapse within 1 year of last dose of previous adjuvant (including neoadjuvant) treatment (except endocrine therapy) and within 1 year before randomization.

• Prior systemic therapy for metastatic disease (except endocrine therapy).

• Prior cumulative dose of doxorubicin of >400 mg/m2, epirubicin dose >800 mg/m^{2, or the equivalent dose for other anthracyclines or derivatives (eg, 72 mg/m}2 of mitoxantrone). If the patient has received more than one anthracycline, then the cumulative dose must not exceed the equivalent of 400 mg/m^2 of doxorubicin.

• Inflammatory breast cancer.

• Active uncontrolled or symptomatic central nervous system metastases.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cancer Center of Central Connecticut	Plainville	Connecticut	United States	06062
2	Cancer Center of Central Connecticut	Southington	Connecticut	United States	06489
3	Florida Cancer Research Institute	Boca Raton	Florida	United States	33428
4	Florida Cancer Research Institute	Plantation	Florida	United States	33324
5	COIBA - Centro de Oncologia e Investigacion Buenos Aires	Berazategui	Buenos Aires	Argentina	B1884BBF
6	Instituto De Oncologia De Rosario	Rosario	Santa FE	Argentina	S2000KZE
7	Centro Medico San Roque	San Miguel de Tucuman	Tucuman	Argentina	T4000IAK
8	Sanatorio de la Providencia	C.a.b.a		Argentina	C1050AAK
9	CRIO - Centro Regional Integrado de Oncologia	Fortaleza	CE	Brazil	60336-045
10	Associacao de Combate ao Cancer em Goias - Hospital Araujo Jorge	Goiania	GO	Brazil	74605070
11	Liga Paranaense de Combate ao Cancer - Hospital Erasto Gaertner	Curitiba	Parana	Brazil	81520-060
12	Instituto do Cancer de Londrina - Hospital do Cancer de Londrina - HCL	Londrina	Parana	Brazil	86015-520
13	Hospital Bruno Born (Sociedade Beneficencia e Caridade de Lajeado)	Lajeado	RIO Grande DO SUL	Brazil	95900-000
14	Associacao Hospital de Caridade Ijui	Ijui	RS	Brazil	98700-000
15	Centro de Pesquisa em Oncologia - Uniao Brasileira de Educacao e Assistencia	Porto Alegre	RS	Brazil	90610-000
16	Centro de Novos Tratamentos Itajai - Clinica de Neoplasias Litoral	Itajai	Santa Catarina	Brazil	88301-215
17	Fundacao Pio XII - Hospital de Cancer de Barretos	Barretos	SAO Paulo	Brazil	14784-400
18	Centro de Pesquisas Oncologicas de Santa Catarina - CEPON	Florianopolis	SC	Brazil	88034-000
19	Centro de Novos Tratamentos Itajai - Clinica de Neoplasias Litoral	Itajai	SC	Brazil	88301-220
20	CEPHO - Centro de Estudos e Pesquisas de Hematologia e Oncologia - Faculdade de Medicina do ABC	Santo Andre	SP	Brazil	09060-650
21	CEPHO - Centro de Estudos e Pesquisas de Hematologia e Oncologia - Faculdade de Medicina do ABC	Santo Andre	SP	Brazil	09060-870
22	Clinica Alemana de Temuco	Temuco	Region DE LA Araucania	Chile	4810297
23	Centro de Investigacion Clinica SIM	Temuco	Region DE LA Araucania	Chile	4810469
24	Administrative office	Temuco	Region DE LA Araucania	Chile	4810561
25	Fresenius Kabi Chile Therapia iv	Santiago	RM	Chile	7780050
26	Hospital Clinico Vina Del Mar	Vina del Mar	V Region	Chile	2520612
27	Instituto Oncologico, Clinica Renaca	Vina del Mar	V Region	Chile	2540364
28	Hospital Naval Almirante Nef	V Region		Chile
29	Instituto Oncologico Clinica Renaca	V Region		Chile
30	Onkologicka klinika VFN a 1. LF UK, Fakultni poliklinika	Praha 2		Czechia	128 08
31	General Hospital of Chania "O Agios Georgios"	Chania	Crete	Greece	73300
32	Interbalkan European Medical Center	Pylaia	Thessaloniki	Greece	57001
33	General Hospital of Athens "Hippokration"	Athens		Greece	11527
34	Bacs-Kiskun Megyei Korhaz, Onkoradiologiai Kozpont	Kecskemet		Hungary	6000
35	Borsod-Abauj-Zemplen Megyei Korhaz, es Egyetemi Oktatokorhaz, Klinikai Onkologiai es Sugarterapias	Miskolc		Hungary	3526
36	Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz - Rendelointezet, Megyei Onkologiai Kozpont	Szolnok		Hungary	5000
37	Markusovszky Egyetemi Oktatokorhaz	Szombathely		Hungary	9700
38	Department of Medicine New Block	Visakhapatnam	Andhra Pradesh	India	530002
39	Manipal Hospital	Bengaluru	Karnataka	India	560017
40	Manipal Centre for Clinical Research	Manipal	Karnataka	India	576104
41	Tata Memorial Centre, Tata Memorial Hospital	Mumbai	Maharashtra	India	400012
42	Shatabdi Super Speciality Hospital	Nashik	Maharashtra	India	422 005
43	Advanced Centre for Treatment Research and Education in Cancer (ACTREC)	Navi Mumbai	Maharashtra	India	401210
44	Deenanath Mangeshkar Hospital & Research Centre	Pune	Maharashtra	India	411 004
45	Sahyadri Clinical Research & Development Centre	Pune	Maharashtra	India	411004
46	Sahyadri Speciality Hospital	Pune	Maharashtra	India	411004
47	Acharya Harihar Regional Cancer Center	Cuttack	Odisha	India	753007
48	Acharya Tulsi Regional Cancer Treatment and Research Institute	Bikaner	Rajasthan	India	334003
49	Meenakshi Mission Hospital and Research Centre	Madurai	Tamil NADU	India	625107
50	MNJ Institute of Oncology & Regional Cancer Center	Hyderabad	Telangana	India	500004
51	National Hospital Organization Nagoya Medical Center	Nagoya	Aichi	Japan	460-0001
52	National Hospital Organization Kyushu Cancer Center	Fukuoka-Shi	Fukuoka	Japan	811-1395
53	Japan Community Health care Organization Kurume General Hospital	Kurume-city	Fukuoka	Japan	830-0013
54	Hokkaido University Hospital	Sapporo	Hokkaido	Japan	060-8648
55	Kumamoto University Hospital	Kumamoto-city	Kumamoto	Japan	8608556
56	Saitama Cancer Center Hospital	Kitaadachi-gun	Saitama	Japan	362-0806
57	Tokyo Metropolitan Cancer and Infectious diseases Center Komagome Hospital	Bunkyo-ku	Tokyo	Japan	113-8677
58	National Hospital Organization Tokyo Medical Center	Meguro-Ku	Tokyo	Japan	152-8902
59	Showa University Hospital	Shinagawa-ku	Tokyo	Japan	142-8666
60	Chiba Cancer Center	Chiba		Japan	260-8717
61	Hakuaikai Medical Corporation Sagara Hospital	Kagoshima		Japan	892-0833
62	Niigata Cancer Center Hospital	Niigata		Japan	951-8566
63	Nakanoshima Osaka Breast Clinic	Osaka		Japan	553-0003
64	Osaka Breast Clinic	Osaka		Japan	553-0003
65	Shizuoka General Hospital	Shizuoka		Japan	420-8527
66	Chungbuk National University Hospital	Cheongju-si	Chungcheongbuk-do	Korea, Republic of	28644
67	Ulsan University Hospital	Ulsan	Korea	Korea, Republic of	44033
68	Pusan National University Hospital	Busan		Korea, Republic of	49241
69	Kyungpook National University Chilgok Hospital	Daegu		Korea, Republic of	41404
70	National Cancer Centre	Goyang-si		Korea, Republic of	10408
71	Korea University Anam Hospital	Seoul		Korea, Republic of	02841
72	Severance Hospital, Yonsei University Health System	Seoul		Korea, Republic of	03722
73	Korea University Guro Hospital	Seoul		Korea, Republic of	08308
74	P.Stradins Clinical University Hospital	Riga		Latvia	LV 1002
75	Instituto Nacional de Cancerologia	Mexico City	Distrito Federal	Mexico	14080
76	Consultorio dentro de la Torre Medica Dalinde (Oncologia Medica)	Mexico	Distrito Federal	Mexico	06760
77	Inter Hosp S.A. de C.V. "Centro Medico Dalinde"	Mexico	Distrito Federal	Mexico	06760
78	Oaxaca Site Management Organization S.C.	Oaxaca		Mexico	68000
79	Cancerologia de Queretaro S.C.	Queretaro		Mexico	76090
80	Hospital Militar Central	Lima		Peru	11
81	INNPARES	Lima		Peru	11
82	Resocentro	Lima		Peru	18
83	Clinica Anglo Americana	Lima		Peru	27
84	Instituto de Oncologia y Radioterapia de la Clinica Ricardo Palma	Lima		Peru	27
85	Radiologos S.R.L.	Lima		Peru	27
86	Instituto Nacional de Enfermedades Neoplasicas	Lima		Peru	34
87	Siglo XXI	Lima		Peru	41
88	Resocentro	Lima		Peru	Lima 18
89	Siglo XXI	Lima		Peru	Lima 41
90	Cebu Doctors' University Hospital	Cebu City	Cebu	Philippines	6000
91	Cardinal Santos Medical Center	San Juan City	Mentro Manila	Philippines	1502
92	Manila Doctors Hospital	Manila	Metro Manila	Philippines	1000
93	Veterans Memorial Medical Center	Quezon City	Metro Manila	Philippines	1110
94	University of Philippines Manila-Philippine General Hospital	Manila	NCR	Philippines	1000
95	The Medical City	Pasig City	NCR	Philippines	1605
96	St. Luke's Medical Center	Quezon City	NCR	Philippines	1102
97	The Research Institute at Perpetual Succor Hospital	Cebu City	Region VII	Philippines	6000
98	Manila Doctors Hospital	Manila		Philippines	1000
99	COPERNICUS Podmiot Leczniczy Sp. z o.o. Wojewodzkie Centrum Onkologii	Gdansk		Poland	80-219
100	Szpitale Pomorskie Sp. z o.o. Oddzial Onkologii i Radioterapii	Gdynia		Poland	81-519
101	Centrum Terapii Wspolczesnej	Lodz		Poland	90-242
102	SPZOZ MSW z Warminsko-Mazurskim Centrum Onkologii w Olsztynie, Oddzial Kliniczny Chemioterapii	Olsztyn		Poland	10-228
103	MRUKMED. Lekarz Beata Madej Mruk i Partner. Sp. p. Oddzial nr 1 w Rzeszowie	Rzeszow		Poland	35-085
104	Magodent Sp. z o.o. Oddzial Onkologii Klinicznej/Chemioterapii	Warszawa		Poland	03-291
105	Hospital de Braga	Braga		Portugal	4710 243
106	Hospital CUF Descobertas	Lisboa		Portugal	1998-018
107	Institutul Oncologic Prof. Dr. Ion Chiricuta	Cluj-Napoca	Cluj	Romania	400015
108	S.C. Medisprof S.R.L	Cluj-Napoca	Cluj	Romania	400641
109	Centrul de Oncologie Sf. Nectarie	Craiova	Dolj	Romania	200347
110	SC Oncolab SRL, Oncologie	Craiova	Jud Dolj	Romania	200385
111	Spitalul Universitar de Urgenta, Departamentul Oncologie Medicala	Bucuresti		Romania	050098
112	Spitalul Clinic Judetean de Urgenta Sibiu	Sibiu		Romania	550245
113	Spitalul Judetean de Urgenta "Sf.Ioan cel Nou", Sectia Oncologie	Suceava		Romania	720237
114	Spitalul Clinic Municipal de Urgenta Timisoara, Sectia Clinica Oncologie Medicala	Timisoara		Romania	300595
115	Republic Clinical Hospital of Emergency Care	Grozny	Chechenkaya Republic	Russian Federation	364020
116	State Healthcare Institution Kursk Regional Oncological Dispensary of the Healthcare Committee	Kislino Settlement	Kursk	Russian Federation	305524
117	State Budgetary Healthcare Institution "Leningrad Regional Oncological Dispensary"	Kuzmolovo, Vsevolozhskiy	Leningrad Region	Russian Federation	188663
118	FSBSI Russian Cancer Research Center n.a. N.N.Blokhin	Moscow	NAP	Russian Federation	115478
119	GBUZ of Perm region "Perm regional oncology dispensary"	Perm	NAP	Russian Federation	614066
120	Federal State Budgetary Institution ¿National Medical Research Oncology Centre named after N.N.	Saint-Petersburg	Pos.pesochny	Russian Federation	197758
121	State Healthcare Institution, Republican Clinical Oncology Dispensary of the Ministry of	Ufa	Republic OF Bashkortostan	Russian Federation	450054
122	GBUZ Republican Clinical Hospital n.a. G.F. Kuvatova	Ufa	Republic OF Baskortostan	Russian Federation	450005
123	Republican Clinical Oncology Dispensary of the Ministry of Healthcare of Baskortostan Republic	Ufa	Republic OF Baskortostan	Russian Federation	450054
124	State Budgetary Healthcare Institution ''Republic Oncological Dispensary''	Petrozavodsk	Republic OF Karelia	Russian Federation	185002
125	State budget institution of healthcare of Mordovia Republic "Republic Oncology Dispensary"	Saransk	Republic OF Mordovia	Russian Federation	430032
126	Rostov Research Institute of Oncology	Rostov-on-Don	Rostov Region	Russian Federation	344037
127	Private medical institution Euromedservice	Pushkin	Saint Petersburg	Russian Federation	196603
128	Saint-Petersburg Clinical Research Center of Specialized Types of Medical Care (Oncology)	Poselok Pesochny	Saint-petersburg	Russian Federation	197758
129	LLC Medekspert	Kislovodsk	Stavropol Region	Russian Federation	357700
130	Federal State Budgetary Healthcare Institution of "Clinical Hospital #101 of Federal Medical and	Lermontov	Stavropol Region	Russian Federation	357340
131	Centre of Specialized kinds of Medical Care of Pyatigorsk city	Pyatigorsk	Stavropol Region	Russian Federation	357502
132	State Budgetary Healthcare Institution of Stavropol Region Pyatigorsk Oncology Dispensary	Pyatigorsk	Stavropol Region	Russian Federation	357502
133	LLC Novaya Clinica	Pyatigorsk	Stavropol Region	Russian Federation	357519
134	Pyatigorsk City Hospital #2	Pyatigorsk	Stavropol Region	Russian Federation	357538
135	Stavropol Regional Hospital for War Veterans	Pyatigorsk	Stavropol Region	Russian Federation	357563
136	State Budgetary Healthcare Institution Volgograd Regional Clinical Oncology Dispensary	Volzhskiy	Volgograd Region	Russian Federation	404130
137	GBUZ Arkhangelsk Regional Clinical Oncological dispensary	Arkhangelsk		Russian Federation	163045
138	State Budgetary Healthcare Institution "Chelyabinsk Regional Clinical Oncological Dispensary"	Chelyabinsk		Russian Federation	454087
139	"Regional Budgetary Healthcare Institution ""Ivanovo Regional Oncology Dispensary"""	Ivanovo		Russian Federation	153040
140	SBIH of Kaluga Region "Kaluga Regional Clinical Oncology Dispensary"	Kaluga		Russian Federation	248007
141	GBUZ "Regional Oncology Dispensary #2"	Magnitogorsk		Russian Federation	455001
142	Federal State Budgetary Institution "Russian Oncological Scientific Center n.a. N.N. Blokhin" of	Moscow		Russian Federation	115478
143	LLC VitaMed	Moscow		Russian Federation	121309
144	LLC VitaMed	Moscow		Russian Federation	129515
145	State Budgetary Healthcare Institution "Nizhniy Novgorod Regional Oncological Dispensary"	Nizhniy Novgorod		Russian Federation	603081
146	"BIH of Omsk Region ""Clinical oncological dispensary"""	Omsk		Russian Federation	644046
147	Budgetary Institution of Healthcare of Orel region "Orel oncological dispensary"	Orel		Russian Federation	302020
148	SBEI HPE RyazSMU of MoH of the Russian Federation based on SBI of Ryazan Region "Regional CLinical	Ryazan		Russian Federation	390011
149	SBEI of HPE "First Saint Petersburg State Medical University	Saint Petersburg		Russian Federation	197022
150	SBI "North-Western State Medical University n.a. I. I. Mechnikov" of the MoH of the Russian	Saint-Petersburg		Russian Federation	195067
151	Non-state healthcare agency Road Clinical Hospital PLC Russian Railways	Saint-Petersburg		Russian Federation	195271
152	Saint-Petersburg State Budgetary Healthcare Institution "Oncological Dispensary of Moscow District"	Saint-Petersburg		Russian Federation	196247
153	Non-State Healthcare Institution "Road Clinical Hospital at Saratov II Station"	Saratov		Russian Federation	410004
154	State Budgetary Healthcare Institution of Stavropol region "Stavropol regional clinical oncology	Stavropol		Russian Federation	355047
155	Institute for Oncology and Radiology of Serbia	Belgrade		Serbia	11000
156	Military Medical Academy	Belgrade		Serbia	11000
157	Clinic of Oncology-Clinical Center Nis	Nis		Serbia	18000
158	Oncology Institute of Vojvodina	Sremska Kamenica		Serbia	21204
159	Onkologicky ustav sv. Alzbety, s.r.o.	Bratislava		Slovakia	812 50
160	Narodny Onkologicky Ustav	Bratislava		Slovakia	833 10
161	GVI Oncology, Langenhoven Drive Oncology Centre	Port Elizabeth	Eastern CAPE	South Africa	6045
162	wits Clinical Research	Joannesburg	Gauteng	South Africa	2193
163	The Medical Oncology Centre of Rosebank	Johannesburg	Gauteng	South Africa	2196
164	Sandton Oncology Centre	Johannesburg	Gauteng	South Africa	2199
165	*Department of Medical Oncology, University of Pretoria & Steve Biko Academic Hospitals Complex	Pretoria	Gauteng	South Africa	0002
166	Eastleigh Breast Care Centre	Pretoria	Gauteng	South Africa	0081
167	Cape Town Oncology Trials	Kraaifontein	Western CAPE	South Africa	7570
168	GVI Rondebosch Oncology Centre-Rondebosch Medical Centre	Rondebosch	Western CAPE	South Africa	7700
169	National Cancer Institute	Ratchathewi	Bangkok	Thailand	10400
170	Udonthani Cancer Hospital	Amphur Muang	Udonthani	Thailand	41330
171	Faculty of Medicine, Chulongkorn University, Medical Oncology Unit	Bangkok		Thailand	10330
172	Baskent University School of Medicine Adana Hospital	Adana		Turkey	01120
173	Hacettepe Universitesi Tip Fakultesi	Ankara		Turkey	06100
174	Uludag Universitesi Tip Fakultesi Ic Hastaliklari Anabilim Dali	Bursa		Turkey	16059
175	Dicle University Medical Faculty	Diyarbakir		Turkey	21080
176	Gaziantep University Medical Faculty	Gaziantep		Turkey	27310
177	Istanbul Universitesi Onkoloji Enstitusu	Istanbul		Turkey	34093
178	Municipal Institution "Chernivtsi Regional Clinical Oncology Center", Outpatient Department	Chernivtsi		Ukraine	58013
179	Municipal Non-Profit Enterprise City Clinical Hospital No.4of Dnipro Regional Council, Department of	Dnipro		Ukraine	49102
180	SI Institute of Medical Radiology n.a.S.P. Ilrygoriev of National Academy of Medical Science of	Kharkiv		Ukraine	61024
181	Communal Non-Profit Enterprise "Regional Center of Oncology"	Kharkiv		Ukraine	61070
182	Khmelnytskyi Regional Oncologic Dispensary	Khmelnytskyi		Ukraine	29009
183	Municipal Enterprise 'Kryvyi Rih Oncology Dispensary of Dnipropetrovsk Regional Council'	Kryvyi Rih		Ukraine	50048
184	Municipal Non-Profit Enterprise of Kyiv Regional Council "Kyiv Regional Oncology Dispensary"	Kyiv		Ukraine	04107
185	Lviv State Oncologic Regional Treatment and Diagnostic Center	Lviv		Ukraine	79031
186	Municipal Institution Odesa Regional Clinical Hospital, Mammology Center	Odesa		Ukraine	65025
187	Zakarpattia Regional Clinical Oncological Center	Uzhgorod		Ukraine	88014
188	Municipal Non-profit Enterprise Podilsk Regional Oncology Centre of Vinnytsia Regional Council	Vinnytsia		Ukraine	21029

Sponsors and Collaborators

• Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Related Info

Publications

None provided.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT01989676
• Other Study ID Numbers: B3271002; REFLECTIONS B327-02; 2013-001352-34; B3271002
• First Posted: Nov 21, 2013
• Last Update Posted: Jul 6, 2021
• Last Verified: Jun 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Pfizer: Phase 3; trastuzumab; Breast Neoplasms
• Additional relevant MeSH terms: Breast Neoplasms; Paclitaxel; Albumin-Bound Paclitaxel; Trastuzumab

Study Results

Participant Flow

Recruitment Details	A total of 707 participants were randomized to the study. Of these, 5 participants were randomized but did not receive the study drug.
Pre-assignment Detail	Participants who fulfilled the inclusion/exclusion criteria were randomly assigned to 1 of the 2 treatments of this study.

Arm/Group Title	PF-05280014	Trastuzumab-EU
Arm/Group Description	Participants with human epidermal growth factor receptor 2 (HER2)-positive breast cancer received PF-05280014 on Days 1, 8, 15 and 22 of each 28-day cycle followed by paclitaxel on Days 1, 8 and 15 of each 28-day cycle both as intravenous (IV) infusions until the end of the study. The first infusion of PF-05280014 was 4 mg/kg over 90 minutes on Cycle 1 Day 1. Subsequent weekly infusions of PF-05280014 were 2 mg/kg over 30 to 90 minutes. Paclitaxel was administered at a dose of 80 mg/m^2 over 60 minutes. Following completion of the paclitaxel administration period and beginning no earlier than Week 33 of the study, the PF-05280014 could be changed at the discretion of the investigator to every 3 weeks at a dose of 6 mg/kg infused over 30 to 90 minutes depending on tolerability.	Participants with HER2-positive breast cancer received trastuzumab-EU on Days 1, 8, 15 and 22 of each 28-day cycle followed by paclitaxel on Days 1, 8 and 15 of each 28-day cycle both as IV infusions until the end of the study. The first infusion of trastuzumab-EU was 4 mg/kg over 90 minutes on Cycle 1 Day 1. Subsequent weekly infusions of trastuzumab-EU were 2 mg/kg over 30 to 90 minutes. Paclitaxel was administered at a dose of 80 mg/m^2 over 60 minutes. Following completion of the paclitaxel administration period and beginning no earlier than Week 33 of the study, the trastuzuamab-EU could be changed at the discretion of the investigator to every 3 weeks at a dose of 6 mg/kg infused over 30 to 90 minutes depending on tolerability.
Period Title: Overall Study
STARTED	352	355
Treated	349	353
COMPLETED	234	217
NOT COMPLETED	118	138

Baseline Characteristics

Arm/Group Title	PF-05280014	Trastuzumab-EU	Total
Arm/Group Description	Participants with human epidermal growth factor receptor 2 (HER2)-positive breast cancer received PF-05280014 on Days 1, 8, 15 and 22 of each 28-day cycle followed by paclitaxel on Days 1, 8 and 15 of each 28-day cycle both as intravenous (IV) infusions until the end of the study. The first infusion of PF-05280014 was 4 mg/kg over 90 minutes on Cycle 1 Day 1. Subsequent weekly infusions of PF-05280014 were 2 mg/kg over 30 to 90 minutes. Paclitaxel was administered at a dose of 80 mg/m^2 over 60 minutes. Following completion of the paclitaxel administration period and beginning no earlier than Week 33 of the study, the PF-05280014 could be changed at the discretion of the investigator to every 3 weeks at a dose of 6 mg/kg infused over 30 to 90 minutes depending on tolerability.	Participants with HER2-positive breast cancer received trastuzumab-EU on Days 1, 8, 15 and 22 of each 28-day cycle followed by paclitaxel on Days 1, 8 and 15 of each 28-day cycle both as IV infusions until the end of the study. The first infusion of trastuzumab-EU was 4 mg/kg over 90 minutes on Cycle 1 Day 1. Subsequent weekly infusions of trastuzumab-EU were 2 mg/kg over 30 to 90 minutes. Paclitaxel was administered at a dose of 80 mg/m^2 over 60 minutes. Following completion of the paclitaxel administration period and beginning no earlier than Week 33 of the study, the trastuzuamab-EU could be changed at the discretion of the investigator to every 3 weeks at a dose of 6 mg/kg infused over 30 to 90 minutes depending on tolerability.	Total of all reporting groups
Overall Participants	349	353	702
Age, Customized (Number) [Number]
<18	0 0%	0 0%	0 0%
18 to 64	283 81.1%	292 82.7%	575 81.9%
65 to 84	66 18.9%	60 17%	126 17.9%
≥85	0 0%	1 0.3%	1 0.1%
Sex: Female, Male (Count of Participants)
Female	349 100%	353 100%	702 100%
Male	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Objective Response Rate (ORR) Derived From Central Radiology Assessments: ITT Population
Description	ORR was defined as the percentage of participants who achieved complete response (CR, complete disappearance of all target lesions with the exception of nodal disease; all target nodes must have decreased to normal size [short axis <10 mm]) or partial response (PR, >=30% decrease from baseline of the sum of diameters (SOD) of all target measurable lesions; the short diameter was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions) by Week 25 of the study and confirmed on a follow-up assessment (Week 33+/-14 days), based on the assessments of the central radiology review in accordance with RECIST 1.1.
Time Frame	From the date of randomization until all participants had either completed the Week 33 tumor assessment or discontinued study drug earlier than the Week 33 visit

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all participants who were randomized to study drug.

Arm/Group Title	PF-05280014	Trastuzumab-EU
Arm/Group Description	Participants with human epidermal growth factor receptor 2 (HER2)-positive breast cancer received PF-05280014 on Days 1, 8, 15 and 22 of each 28-day cycle followed by paclitaxel on Days 1, 8 and 15 of each 28-day cycle both as intravenous (IV) infusions until the end of the study. The first infusion of PF-05280014 was 4 mg/kg over 90 minutes on Cycle 1 Day 1. Subsequent weekly infusions of PF-05280014 were 2 mg/kg over 30 to 90 minutes. Paclitaxel was administered at a dose of 80 mg/m^2 over 60 minutes. Following completion of the paclitaxel administration period and beginning no earlier than Week 33 of the study, the PF-05280014 could be changed at the discretion of the investigator to every 3 weeks at a dose of 6 mg/kg infused over 30 to 90 minutes depending on tolerability.	Participants with HER2-positive breast cancer received trastuzumab-EU on Days 1, 8, 15 and 22 of each 28-day cycle followed by paclitaxel on Days 1, 8 and 15 of each 28-day cycle both as IV infusions until the end of the study. The first infusion of trastuzumab-EU was 4 mg/kg over 90 minutes on Cycle 1 Day 1. Subsequent weekly infusions of trastuzumab-EU were 2 mg/kg over 30 to 90 minutes. Paclitaxel was administered at a dose of 80 mg/m^2 over 60 minutes. Following completion of the paclitaxel administration period and beginning no earlier than Week 33 of the study, the trastuzuamab-EU could be changed at the discretion of the investigator to every 3 weeks at a dose of 6 mg/kg infused over 30 to 90 minutes depending on tolerability.
Measure Participants	352	355
Number (95% Confidence Interval) [percentage of participants]	62.5 17.9%	66.5 18.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PF-05280014, Trastuzumab-EU
	Comments	Risk Ratio and associated 95% confidence interval (CI) are unstratified and based on the Miettinen and Nurminen method.
	Type of Statistical Test	Equivalence
	Comments	The hypothesis to be tested in this study was that the risk ratio of ORR of PF-05280014 versus that of trastuzumab-EU by Week 25 (+/-14 days) was within a pre-specified margin of 0.80 to 1.25.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.940
	Confidence Interval	(2-Sided) 95%; 0.842 to 1.049
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	One-year Progression-Free Survival (PFS) Rate Derived From Central Radiology Assessments: ITT Population
Description	One-year PFS rate was analyzed based on the time from date of randomization to first documentation of progressive disease (PD), or death due to any cause in the absence of documented PD, based on the assessments of the central radiology review in accordance with RECIST 1.1. PD was defined for target disease as at least a 20% increase in sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum was observed during therapy) with a minimum absolute increase of 5 mm. For non-target disease: PD was defined as unequivocal progression of pre-existing lesions and if overall tumor burden increased sufficiently to merit discontinuation of therapy; appearance of any new unequivocal malignant lesion was also considered PD. The 95% CI for the median time to event was based on the Brookmeyer and Crowley method.
Time Frame	From the date of randomization until 378 days post-randomization

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all participants who were randomized to study drug.

Arm/Group Title	PF-05280014	Trastuzumab-EU
Arm/Group Description	Participants with human epidermal growth factor receptor 2 (HER2)-positive breast cancer received PF-05280014 on Days 1, 8, 15 and 22 of each 28-day cycle followed by paclitaxel on Days 1, 8 and 15 of each 28-day cycle both as intravenous (IV) infusions until the end of the study. The first infusion of PF-05280014 was 4 mg/kg over 90 minutes on Cycle 1 Day 1. Subsequent weekly infusions of PF-05280014 were 2 mg/kg over 30 to 90 minutes. Paclitaxel was administered at a dose of 80 mg/m^2 over 60 minutes. Following completion of the paclitaxel administration period and beginning no earlier than Week 33 of the study, the PF-05280014 could be changed at the discretion of the investigator to every 3 weeks at a dose of 6 mg/kg infused over 30 to 90 minutes depending on tolerability.	Participants with HER2-positive breast cancer received trastuzumab-EU on Days 1, 8, 15 and 22 of each 28-day cycle followed by paclitaxel on Days 1, 8 and 15 of each 28-day cycle both as IV infusions until the end of the study. The first infusion of trastuzumab-EU was 4 mg/kg over 90 minutes on Cycle 1 Day 1. Subsequent weekly infusions of trastuzumab-EU were 2 mg/kg over 30 to 90 minutes. Paclitaxel was administered at a dose of 80 mg/m^2 over 60 minutes. Following completion of the paclitaxel administration period and beginning no earlier than Week 33 of the study, the trastuzuamab-EU could be changed at the discretion of the investigator to every 3 weeks at a dose of 6 mg/kg infused over 30 to 90 minutes depending on tolerability.
Measure Participants	352	355
Median (95% Confidence Interval) [months]	12.16	12.06

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PF-05280014, Trastuzumab-EU
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.505
	Comments	1-sided log-rank test was used to compare the PFS distribution between the two treatment groups and was stratified by prior trastuzumab exposure (Yes/No) and estrogen receptor (ER) status (ER positive vs. ER negative).
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Cox Proportional Hazard
	Estimated Value	1.00
	Confidence Interval	(2-Sided) 95%; 0.80 to 1.26
	Parameter Dispersion	Type: Value:
	Estimation Comments	The 95% CI for the hazard ratio was based on the Cox's proportional hazard model.

3. Secondary Outcome

Title	Duration of Response (DOR) Per Central Radiology Assessments: ITT Population
Description	DOR:time from first documentation of objective response (CR or PR) to first documentation of PD/death due to any cause in absence of documented PD, based on central radiology review. As per RECIST v1.1, CR:complete disappearance of all target lesions with exception of nodal disease; all target nodes reduced in short axis <10 mm. PR: >=30% decrease from baseline of SOD of target lesions; short diameter used in sum for target nodes,longest diameter used in sum for other target lesions. PD for target disease:at least 20% increase in SOD of target lesions above smallest sum observed (over baseline if no decrease in sum observed) with minimum absolute increase of 5 mm. For non-target disease:unequivocal progression of pre-existing lesions and if overall tumor burden increased sufficiently to merit discontinuation of therapy; appearance of any new unequivocal malignant lesion was also considered PD. The 95% CI for median time to event was based on the Brookmeyer and Crowley method.
Time Frame	From the date of randomization until 378 days post-randomization

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all participants who were randomized to study drug. Here "Overall number of participants analyzed" signifies participants evaluable for this outcome measure.

Arm/Group Title	PF-05280014	Trastuzumab-EU
Arm/Group Description	Participants with human epidermal growth factor receptor 2 (HER2)-positive breast cancer received PF-05280014 on Days 1, 8, 15 and 22 of each 28-day cycle followed by paclitaxel on Days 1, 8 and 15 of each 28-day cycle both as intravenous (IV) infusions until the end of the study. The first infusion of PF-05280014 was 4 mg/kg over 90 minutes on Cycle 1 Day 1. Subsequent weekly infusions of PF-05280014 were 2 mg/kg over 30 to 90 minutes. Paclitaxel was administered at a dose of 80 mg/m^2 over 60 minutes. Following completion of the paclitaxel administration period and beginning no earlier than Week 33 of the study, the PF-05280014 could be changed at the discretion of the investigator to every 3 weeks at a dose of 6 mg/kg infused over 30 to 90 minutes depending on tolerability.	Participants with HER2-positive breast cancer received trastuzumab-EU on Days 1, 8, 15 and 22 of each 28-day cycle followed by paclitaxel on Days 1, 8 and 15 of each 28-day cycle both as IV infusions until the end of the study. The first infusion of trastuzumab-EU was 4 mg/kg over 90 minutes on Cycle 1 Day 1. Subsequent weekly infusions of trastuzumab-EU were 2 mg/kg over 30 to 90 minutes. Paclitaxel was administered at a dose of 80 mg/m^2 over 60 minutes. Following completion of the paclitaxel administration period and beginning no earlier than Week 33 of the study, the trastuzuamab-EU could be changed at the discretion of the investigator to every 3 weeks at a dose of 6 mg/kg infused over 30 to 90 minutes depending on tolerability.
Measure Participants	224	238
Median (95% Confidence Interval) [months]	11.27	10.58

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PF-05280014, Trastuzumab-EU
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.304
	Comments	1-sided log-rank test was used to compare the DOR distribution between the two treatment groups and was stratified by prior trastuzumab exposure (Yes/No) and ER status (ER positive vs. ER negative).
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Cox Proportional Hazard
	Estimated Value	0.92
	Confidence Interval	(2-Sided) 95%; 0.67 to 1.27
	Parameter Dispersion	Type: Value:
	Estimation Comments	The 95% CI for the hazard ratio was based on the Cox's proportional hazard model.

4. Secondary Outcome

Title	Overall Survival: ITT Population
Description	Overall survival was analyzed based on the time from date of randomization to the date of death due to any cause. Participants last known to be alive were censored on the date of last contact. The 95% CI for the median time to event was based on the Brookmeyer and Crowley Method.
Time Frame	From the date of randomization until end of study (approximately 6 years)

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all participants who were randomized to study drug.

Arm/Group Title	PF-05280014	Trastuzumab-EU
Arm/Group Description	Participants with human epidermal growth factor receptor 2 (HER2)-positive breast cancer received PF-05280014 on Days 1, 8, 15 and 22 of each 28-day cycle followed by paclitaxel on Days 1, 8 and 15 of each 28-day cycle both as intravenous (IV) infusions until the end of the study. The first infusion of PF-05280014 was 4 mg/kg over 90 minutes on Cycle 1 Day 1. Subsequent weekly infusions of PF-05280014 were 2 mg/kg over 30 to 90 minutes. Paclitaxel was administered at a dose of 80 mg/m^2 over 60 minutes. Following completion of the paclitaxel administration period and beginning no earlier than Week 33 of the study, the PF-05280014 could be changed at the discretion of the investigator to every 3 weeks at a dose of 6 mg/kg infused over 30 to 90 minutes depending on tolerability.	Participants with HER2-positive breast cancer received trastuzumab-EU on Days 1, 8, 15 and 22 of each 28-day cycle followed by paclitaxel on Days 1, 8 and 15 of each 28-day cycle both as IV infusions until the end of the study. The first infusion of trastuzumab-EU was 4 mg/kg over 90 minutes on Cycle 1 Day 1. Subsequent weekly infusions of trastuzumab-EU were 2 mg/kg over 30 to 90 minutes. Paclitaxel was administered at a dose of 80 mg/m^2 over 60 minutes. Following completion of the paclitaxel administration period and beginning no earlier than Week 33 of the study, the trastuzuamab-EU could be changed at the discretion of the investigator to every 3 weeks at a dose of 6 mg/kg infused over 30 to 90 minutes depending on tolerability.
Measure Participants	352	355
Median (95% Confidence Interval) [months]	NA	NA

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PF-05280014, Trastuzumab-EU
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.339
	Comments	1-sided log-rank test was used to compare the OS distribution between the two treatment groups and was stratified by prior trastuzumab exposure (Yes/No) and ER status (ER positive vs. ER negative).
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Cox Proportional Hazard
	Estimated Value	0.929
	Confidence Interval	(2-Sided) 95%; 0.656 to 1.316
	Parameter Dispersion	Type: Value:
	Estimation Comments	The 95% CI for the hazard ratio was based on the Cox's proportional hazard model.

5. Secondary Outcome

Title	Serum Peak Concentration of PF-05280014 at Selected Cycles: Pharmacokinetics (PK) Population
Description	Human PK serum samples were analyzed for concentrations of PF-05280014 using a validated, sensitive, and specific enzyme-linked immunosorbent assay (ELISA).
Time Frame	1 hour post end of infusion on Day 1 of Cycles 1 and 5

Outcome Measure Data

Analysis Population Description

PK population was used for analysis, included all participants who received PF-05280014 or trastuzumab-EU and had no major protocol deviations that influenced PK assessments, and had at least 1 post dose concentration measurement. Here "number analyzed (n)" signifies participants evaluable at specified time points only.

Arm/Group Title	PF-05280014
Arm/Group Description	Participants with human epidermal growth factor receptor 2 (HER2)-positive breast cancer received PF-05280014 on Days 1, 8, 15 and 22 of each 28-day cycle followed by paclitaxel on Days 1, 8 and 15 of each 28-day cycle both as intravenous (IV) infusions until the end of the study. The first infusion of PF-05280014 was 4 mg/kg over 90 minutes on Cycle 1 Day 1. Subsequent weekly infusions of PF-05280014 were 2 mg/kg over 30 to 90 minutes. Paclitaxel was administered at a dose of 80 mg/m^2 over 60 minutes. Following completion of the paclitaxel administration period and beginning no earlier than Week 33 of the study, the PF-05280014 could be changed at the discretion of the investigator to every 3 weeks at a dose of 6 mg/kg infused over 30 to 90 minutes depending on tolerability.
Measure Participants	349
Cycle 1 Day 1	89.85
Cycle 5 Day 1	95.70

6. Secondary Outcome

Title	Serum Peak Concentration of Trastuzumab-EU at Selected Cycles: PK Population
Description	Human PK serum samples were analyzed for concentrations of trastuzumab-EU using a validated, sensitive, and specific ELISA.
Time Frame	1 hour post end of infusion on Day 1 of Cycles 1 and 5

Outcome Measure Data

Analysis Population Description

PK population was used for analysis, included all participants who received PF-05280014 or trastuzumab-EU and had no major protocol deviations that influenced PK assessments, and had at least 1 post dose concentration measurement. Here "n" signifies participants evaluable at specified time points only.

Arm/Group Title	Trastuzumab-EU
Arm/Group Description	Participants with HER2-positive breast cancer received trastuzumab-EU on Days 1, 8, 15 and 22 of each 28-day cycle followed by paclitaxel on Days 1, 8 and 15 of each 28-day cycle both as IV infusions until the end of the study. The first infusion of trastuzumab-EU was 4 mg/kg over 90 minutes on Cycle 1 Day 1. Subsequent weekly infusions of trastuzumab-EU were 2 mg/kg over 30 to 90 minutes. Paclitaxel was administered at a dose of 80 mg/m^2 over 60 minutes. Following completion of the paclitaxel administration period and beginning no earlier than Week 33 of the study, the trastuzuamab-EU could be changed at the discretion of the investigator to every 3 weeks at a dose of 6 mg/kg infused over 30 to 90 minutes depending on tolerability.
Measure Participants	353
Cycle 1 Day 1	89.70
Cycle 5 Day 1	94.40

7. Secondary Outcome

Title	Serum Trough (Pre-dose) Concentration of PF-05280014 at Selected Cycles: PK Population
Description	Human PK serum samples were analyzed for concentrations of PF-05280014 using a validated, sensitive, and specific ELISA.
Time Frame	Pre-dose on Day 1 of Cycles 1, 3, 4, 5, 7, 8, 11, 14, 17 and Day 8 of Cycles 1 and 5

Outcome Measure Data

Analysis Population Description

PK population.Here "n" signifies participants evaluable at specified time points only.The Cycle 17 Day 1 (C17D1) samples summarized previously at PCD (Week 33) fell outside of cut-off used for final analysis (Week 53), to limit data for up to 1-year post randomization, which was more conservative from previous Week 33 analysis. While comparing data between Week 33 and Week 53, there was a significant drop off in number of samples summarized at C17D1 and was down to zero for this outcome measure.

Arm/Group Title	PF-05280014
Arm/Group Description	Participants with human epidermal growth factor receptor 2 (HER2)-positive breast cancer received PF-05280014 on Days 1, 8, 15 and 22 of each 28-day cycle followed by paclitaxel on Days 1, 8 and 15 of each 28-day cycle both as intravenous (IV) infusions until the end of the study. The first infusion of PF-05280014 was 4 mg/kg over 90 minutes on Cycle 1 Day 1. Subsequent weekly infusions of PF-05280014 were 2 mg/kg over 30 to 90 minutes. Paclitaxel was administered at a dose of 80 mg/m^2 over 60 minutes. Following completion of the paclitaxel administration period and beginning no earlier than Week 33 of the study, the PF-05280014 could be changed at the discretion of the investigator to every 3 weeks at a dose of 6 mg/kg infused over 30 to 90 minutes depending on tolerability.
Measure Participants	349
Cycle 1 Day 1	0.00
Cycle 1 Day 8	27.90
Cycle 3 Day 1	48.20
Cycle 4 Day 1	53.50
Cycle 5 Day 1	57.00
Cycle 5 Day 8	57.40
Cycle 7 Day 1	60.50
Cycle 8 Day 1	62.25
Cycle 11 Day 1	54.65
Cycle 14 Day 1	50.70

8. Secondary Outcome

Title	Serum Trough (Pre-dose) Concentration of Trastuzumab-EU at Selected Cycles: PK Population
Description	Human PK serum samples were analyzed for concentrations of trastuzumab-EU using a validated, sensitive, and specific ELISA.
Time Frame	Pre-dose on Day 1 of Cycles 1, 3, 4, 5, 7, 8, 11, 14, 17 and Day 8 of Cycles 1 and 5

Outcome Measure Data

Analysis Population Description

PK population was used for analysis, included all participants who received PF-05280014 or trastuzumab-EU and had no major protocol deviations that influenced PK assessments, and had at least 1 post dose concentration measurement. Here "n" signifies participants evaluable at specified time points only.

Arm/Group Title	Trastuzumab-EU
Arm/Group Description	Participants with HER2-positive breast cancer received trastuzumab-EU on Days 1, 8, 15 and 22 of each 28-day cycle followed by paclitaxel on Days 1, 8 and 15 of each 28-day cycle both as IV infusions until the end of the study. The first infusion of trastuzumab-EU was 4 mg/kg over 90 minutes on Cycle 1 Day 1. Subsequent weekly infusions of trastuzumab-EU were 2 mg/kg over 30 to 90 minutes. Paclitaxel was administered at a dose of 80 mg/m^2 over 60 minutes. Following completion of the paclitaxel administration period and beginning no earlier than Week 33 of the study, the trastuzuamab-EU could be changed at the discretion of the investigator to every 3 weeks at a dose of 6 mg/kg infused over 30 to 90 minutes depending on tolerability.
Measure Participants	353
Cycle 1 Day 1	0.00
Cycle 1 Day 8	29.80
Cycle 3 Day 1	50.40
Cycle 4 Day 1	54.35
Cycle 5 Day 1	60.00
Cycle 5 Day 8	61.20
Cycle 7 Day 1	63.00
Cycle 8 Day 1	65.55
Cycle 11 Day 1	57.50
Cycle 14 Day 1	54.60
Cycle 17 Day 1	45.10

9. Secondary Outcome

Title	Number of Participants With Positive Anti-Drug Antibodies (ADA) Sample: Safety Population
Description	Two sensitive, specific, and semi-quantitative electrochemiluminescent (ECL) immunoassays, 1 for detecting antibodies against PF-05280014 and the other for detecting antibodies against trastuzumab, were used to analyze ADA samples. Serum samples were first screened for ADA. Any samples that were positive in the screening assay were further analyzed to confirm the positive result and determine the antibody titers. All samples were taken prior to dosing. The number of participants with a positive sample (titer >=1.0) is provided.
Time Frame	Pre-dose on Day 1 of Cycles 1, 3, 5, 8, 11, 14, 17

Outcome Measure Data

Analysis Population Description

Safety population was used for analysis, included all participants who received at least 1 dose of study drug. Here "n" signifies participants evaluable at specified time points only.

Arm/Group Title	PF-05280014	Trastuzumab-EU
Arm/Group Description	Participants with human epidermal growth factor receptor 2 (HER2)-positive breast cancer received PF-05280014 on Days 1, 8, 15 and 22 of each 28-day cycle followed by paclitaxel on Days 1, 8 and 15 of each 28-day cycle both as intravenous (IV) infusions until the end of the study. The first infusion of PF-05280014 was 4 mg/kg over 90 minutes on Cycle 1 Day 1. Subsequent weekly infusions of PF-05280014 were 2 mg/kg over 30 to 90 minutes. Paclitaxel was administered at a dose of 80 mg/m^2 over 60 minutes. Following completion of the paclitaxel administration period and beginning no earlier than Week 33 of the study, the PF-05280014 could be changed at the discretion of the investigator to every 3 weeks at a dose of 6 mg/kg infused over 30 to 90 minutes depending on tolerability.	Participants with HER2-positive breast cancer received trastuzumab-EU on Days 1, 8, 15 and 22 of each 28-day cycle followed by paclitaxel on Days 1, 8 and 15 of each 28-day cycle both as IV infusions until the end of the study. The first infusion of trastuzumab-EU was 4 mg/kg over 90 minutes on Cycle 1 Day 1. Subsequent weekly infusions of trastuzumab-EU were 2 mg/kg over 30 to 90 minutes. Paclitaxel was administered at a dose of 80 mg/m^2 over 60 minutes. Following completion of the paclitaxel administration period and beginning no earlier than Week 33 of the study, the trastuzuamab-EU could be changed at the discretion of the investigator to every 3 weeks at a dose of 6 mg/kg infused over 30 to 90 minutes depending on tolerability.
Measure Participants	349	353
Cycle 1 Day 1 (prior to treatment)	30 8.6%	14 4%
Cycle 3 Day 1	0 0%	0 0%
Cycle 5 Day 1	0 0%	0 0%
Cycle 8 Day 1	0 0%	0 0%
Cycle 11 Day 1	0 0%	0 0%
Cycle 14 Day 1	0 0%	0 0%
Cycle 17 Day 1	0 0%

10. Secondary Outcome

Title	Number of Participants With Positive Neutralizing Antibodies (Nab) Prior to Treatment: Safety Population
Description	Human serum samples testing positive for the presence of ADA (anti-PF-05280014 or anti-trastuzumab-EU) were analyzed for the presence or absence of NAb (neutralizing anti-PF-05280014 or neutralizing anti-trastuzumab-EU antibodies) following a tiered approach using screening and titer determination. The number of participants at baseline (prior to treatment) with a positive NAb sample (titer >=1.48) is provided.
Time Frame	Cycle 1 Day 1 (prior to treatment)

Outcome Measure Data

Analysis Population Description

Safety population was used for analysis, included all participants who received at least 1 dose of study drug.

Arm/Group Title	PF-05280014	Trastuzumab-EU
Arm/Group Description	Participants with human epidermal growth factor receptor 2 (HER2)-positive breast cancer received PF-05280014 on Days 1, 8, 15 and 22 of each 28-day cycle followed by paclitaxel on Days 1, 8 and 15 of each 28-day cycle both as intravenous (IV) infusions until the end of the study. The first infusion of PF-05280014 was 4 mg/kg over 90 minutes on Cycle 1 Day 1. Subsequent weekly infusions of PF-05280014 were 2 mg/kg over 30 to 90 minutes. Paclitaxel was administered at a dose of 80 mg/m^2 over 60 minutes. Following completion of the paclitaxel administration period and beginning no earlier than Week 33 of the study, the PF-05280014 could be changed at the discretion of the investigator to every 3 weeks at a dose of 6 mg/kg infused over 30 to 90 minutes depending on tolerability.	Participants with HER2-positive breast cancer received trastuzumab-EU on Days 1, 8, 15 and 22 of each 28-day cycle followed by paclitaxel on Days 1, 8 and 15 of each 28-day cycle both as IV infusions until the end of the study. The first infusion of trastuzumab-EU was 4 mg/kg over 90 minutes on Cycle 1 Day 1. Subsequent weekly infusions of trastuzumab-EU were 2 mg/kg over 30 to 90 minutes. Paclitaxel was administered at a dose of 80 mg/m^2 over 60 minutes. Following completion of the paclitaxel administration period and beginning no earlier than Week 33 of the study, the trastuzuamab-EU could be changed at the discretion of the investigator to every 3 weeks at a dose of 6 mg/kg infused over 30 to 90 minutes depending on tolerability.
Measure Participants	349	350
Count of Participants [Participants]	20 5.7%	9 2.5%

Adverse Events

Time Frame	Adverse events (AEs) and serious AEs (SAEs) which occurred from the time the participant had taken at least 1 dose of study drug and the time of informed consent, respectively, through 70 days after the last dose of study drug (maximum up to 328 weeks)
Adverse Event Reporting Description	All-cause mortality: The total number of deaths occurred during study are reported for all randomized participants, not only for treated participants, and included deaths which occurred beyond 70 days post last study drug dose (i.e. beyond 328 weeks). SAEs and other AEs: Analysis performed on safety population. The safety population included all participants who received at least 1 dose of study drug.
Arm/Group Title	PF-05280014		Trastuzumab-EU
Arm/Group Description	Participants with human epidermal growth factor receptor 2 (HER2)-positive breast cancer received PF-05280014 on Days 1, 8, 15 and 22 of each 28-day cycle followed by paclitaxel on Days 1, 8 and 15 of each 28-day cycle both as intravenous (IV) infusions until the end of the study. The first infusion of PF-05280014 was 4 mg/kg over 90 minutes on Cycle 1 Day 1. Subsequent weekly infusions of PF-05280014 were 2 mg/kg over 30 to 90 minutes. Paclitaxel was administered at a dose of 80 mg/m^2 over 60 minutes. Following completion of the paclitaxel administration period and beginning no earlier than Week 33 of the study, the PF-05280014 could be changed at the discretion of the investigator to every 3 weeks at a dose of 6 mg/kg infused over 30 to 90 minutes depending on tolerability.		Participants with HER2-positive breast cancer received trastuzumab-EU on Days 1, 8, 15 and 22 of each 28-day cycle followed by paclitaxel on Days 1, 8 and 15 of each 28-day cycle both as IV infusions until the end of the study. The first infusion of trastuzumab-EU was 4 mg/kg over 90 minutes on Cycle 1 Day 1. Subsequent weekly infusions of trastuzumab-EU were 2 mg/kg over 30 to 90 minutes. Paclitaxel was administered at a dose of 80 mg/m^2 over 60 minutes. Following completion of the paclitaxel administration period and beginning no earlier than Week 33 of the study, the trastuzuamab-EU could be changed at the discretion of the investigator to every 3 weeks at a dose of 6 mg/kg infused over 30 to 90 minutes depending on tolerability.
All Cause Mortality
	PF-05280014		Trastuzumab-EU
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	61/349 (17.5%)		67/353 (19%)
Serious Adverse Events
	PF-05280014		Trastuzumab-EU
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	67/349 (19.2%)		69/353 (19.5%)
Blood and lymphatic system disorders
Anaemia	3/349 (0.9%)		2/353 (0.6%)
Leukopenia	1/349 (0.3%)		1/353 (0.3%)
Neutropenia	3/349 (0.9%)		1/353 (0.3%)
Thrombocytopenia	1/349 (0.3%)		1/353 (0.3%)
Cardiac disorders
Atrial fibrillation	2/349 (0.6%)		0/353 (0%)
Cardiac arrest	1/349 (0.3%)		1/353 (0.3%)
Cardiac failure	0/349 (0%)		4/353 (1.1%)
Cardiac failure acute	0/349 (0%)		1/353 (0.3%)
Cardio-respiratory arrest	2/349 (0.6%)		0/353 (0%)
Cardiovascular insufficiency	0/349 (0%)		1/353 (0.3%)
Pericardial effusion	1/349 (0.3%)		0/353 (0%)
Myocardial infarction	1/349 (0.3%)		0/353 (0%)
Ventricular tachycardia	1/349 (0.3%)		0/353 (0%)
Ear and labyrinth disorders
Vertigo	1/349 (0.3%)		0/353 (0%)
Endocrine disorders
Thyroiditis subacute	1/349 (0.3%)		0/353 (0%)
Eye disorders
Macular degeneration	1/349 (0.3%)		0/353 (0%)
Gastrointestinal disorders
Diarrhoea	1/349 (0.3%)		1/353 (0.3%)
Duodenal ulcer haemorrhage	0/349 (0%)		1/353 (0.3%)
Dyspepsia	0/349 (0%)		2/353 (0.6%)
Proctalgia	1/349 (0.3%)		0/353 (0%)
Small intestinal obstruction	1/349 (0.3%)		0/353 (0%)
Ileus	1/349 (0.3%)		0/353 (0%)
General disorders
Cyst rupture	1/349 (0.3%)		0/353 (0%)
Death	0/349 (0%)		1/353 (0.3%)
Disease progression	15/349 (4.3%)		16/353 (4.5%)
Fatigue	1/349 (0.3%)		1/353 (0.3%)
Pyrexia	0/349 (0%)		4/353 (1.1%)
Pain	0/349 (0%)		1/353 (0.3%)
Sudden death	0/349 (0%)		1/353 (0.3%)
Hepatobiliary disorders
Cholecystitis	1/349 (0.3%)		0/353 (0%)
Drug-induced liver injury	0/349 (0%)		1/353 (0.3%)
Immune system disorders
Drug hypersensitivity	1/349 (0.3%)		0/353 (0%)
Hypersensitivity	1/349 (0.3%)		0/353 (0%)
Infections and infestations
Bacteraemia	1/349 (0.3%)		0/353 (0%)
Cellulitis	2/349 (0.6%)		4/353 (1.1%)
Cystitis	1/349 (0.3%)		0/353 (0%)
Device related infection	1/349 (0.3%)		0/353 (0%)
Device related sepsis	0/349 (0%)		1/353 (0.3%)
Lower respiratory tract infection	0/349 (0%)		1/353 (0.3%)
Mastitis	1/349 (0.3%)		0/353 (0%)
Osteomyelitis	1/349 (0.3%)		0/353 (0%)
Peritonitis	1/349 (0.3%)		0/353 (0%)
Pneumonia	6/349 (1.7%)		3/353 (0.8%)
Respiratory tract infection	0/349 (0%)		1/353 (0.3%)
Sepsis	0/349 (0%)		2/353 (0.6%)
Septic shock	2/349 (0.6%)		0/353 (0%)
Staphylococcal sepsis	0/349 (0%)		1/353 (0.3%)
Urinary tract infection	3/349 (0.9%)		2/353 (0.6%)
Wound infection	1/349 (0.3%)		0/353 (0%)
Infected skin ulcer	1/349 (0.3%)		0/353 (0%)
Pharyngotonsillitis	1/349 (0.3%)		0/353 (0%)
Injury, poisoning and procedural complications
Fall	0/349 (0%)		2/353 (0.6%)
Infusion related reaction	1/349 (0.3%)		1/353 (0.3%)
Injury	0/349 (0%)		1/353 (0.3%)
Skin laceration	0/349 (0%)		1/353 (0.3%)
Spinal compression fracture	1/349 (0.3%)		1/353 (0.3%)
Femur fracture	1/349 (0.3%)		1/353 (0.3%)
Hip fracture	0/349 (0%)		1/353 (0.3%)
Road traffic accident	0/349 (0%)		1/353 (0.3%)
Investigations
Ejection fraction decreased	0/349 (0%)		2/353 (0.6%)
Metabolism and nutrition disorders
Dehydration	0/349 (0%)		1/353 (0.3%)
Hyperglycaemia	2/349 (0.6%)		0/353 (0%)
Hypernatraemia	1/349 (0.3%)		0/353 (0%)
Hypokalaemia	4/349 (1.1%)		0/353 (0%)
Tumour lysis syndrome	0/349 (0%)		1/353 (0.3%)
Electrolyte imbalance	1/349 (0.3%)		0/353 (0%)
Musculoskeletal and connective tissue disorders
Back pain	0/349 (0%)		1/353 (0.3%)
Pathological fracture	1/349 (0.3%)		0/353 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant pleural effusion	2/349 (0.6%)		0/353 (0%)
Ovarian germ cell teratoma benign	1/349 (0.3%)		0/353 (0%)
Rectal cancer	1/349 (0.3%)		0/353 (0%)
Uterine leiomyoma	0/349 (0%)		1/353 (0.3%)
Colon cancer	0/349 (0%)		1/353 (0.3%)
Endometrial adenocarcinoma	1/349 (0.3%)		0/353 (0%)
Gastric cancer	1/349 (0.3%)		0/353 (0%)
Nasopharyngeal neoplasm benign	0/349 (0%)		1/353 (0.3%)
Neoplasm progression	2/349 (0.6%)		0/353 (0%)
Nervous system disorders
Cerebral infarction	0/349 (0%)		1/353 (0.3%)
Ischaemic stroke	1/349 (0.3%)		3/353 (0.8%)
Neuropathy peripheral	3/349 (0.9%)		0/353 (0%)
Vocal cord paralysis	1/349 (0.3%)		0/353 (0%)
Cerebral venous sinus thrombosis	1/349 (0.3%)		0/353 (0%)
Cerebrovascular accident	0/349 (0%)		1/353 (0.3%)
Syncope	1/349 (0.3%)		0/353 (0%)
Psychiatric disorders
Affective disorder	0/349 (0%)		1/353 (0.3%)
Suicide attempt	1/349 (0.3%)		0/353 (0%)
Renal and urinary disorders
Acute kidney injury	1/349 (0.3%)		1/353 (0.3%)
Hydronephrosis	0/349 (0%)		1/353 (0.3%)
Reproductive system and breast disorders
Endometrial hyperplasia	0/349 (0%)		2/353 (0.6%)
Metrorrhagia	1/349 (0.3%)		0/353 (0%)
Uterine prolapse	1/349 (0.3%)		0/353 (0%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	0/349 (0%)		1/353 (0.3%)
Bronchospasm	1/349 (0.3%)		0/353 (0%)
Chronic obstructive pulmonary disease	1/349 (0.3%)		0/353 (0%)
Pneumonia aspiration	0/349 (0%)		1/353 (0.3%)
Pneumonitis	1/349 (0.3%)		0/353 (0%)
Pulmonary embolism	5/349 (1.4%)		2/353 (0.6%)
Pulmonary oedema	2/349 (0.6%)		0/353 (0%)
Hypersensitivity pneumonitis	1/349 (0.3%)		0/353 (0%)
Interstitial lung disease	1/349 (0.3%)		0/353 (0%)
Skin and subcutaneous tissue disorders
Angioedema	0/349 (0%)		1/353 (0.3%)
Dermatitis contact	0/349 (0%)		1/353 (0.3%)
Skin disorder	1/349 (0.3%)		0/353 (0%)
Skin ulcer	1/349 (0.3%)		0/353 (0%)
Vascular disorders
Deep vein thrombosis	2/349 (0.6%)		0/353 (0%)
Embolism	0/349 (0%)		1/353 (0.3%)
Hypertension	0/349 (0%)		1/353 (0.3%)
Hypovolaemic shock	0/349 (0%)		1/353 (0.3%)
Hypotension	1/349 (0.3%)		0/353 (0%)
Other (Not Including Serious) Adverse Events
	PF-05280014		Trastuzumab-EU
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	337/349 (96.6%)		334/353 (94.6%)
Blood and lymphatic system disorders
Anaemia	122/349 (35%)		134/353 (38%)
Leukopenia	36/349 (10.3%)		45/353 (12.7%)
Neutropenia	97/349 (27.8%)		94/353 (26.6%)
Thrombocytopenia	18/349 (5.2%)		12/353 (3.4%)
Gastrointestinal disorders
Abdominal pain	14/349 (4%)		32/353 (9.1%)
Constipation	24/349 (6.9%)		31/353 (8.8%)
Diarrhoea	61/349 (17.5%)		65/353 (18.4%)
Nausea	58/349 (16.6%)		70/353 (19.8%)
Stomatitis	23/349 (6.6%)		13/353 (3.7%)
Vomiting	28/349 (8%)		26/353 (7.4%)
Dyspepsia	16/349 (4.6%)		18/353 (5.1%)
General disorders
Asthenia	53/349 (15.2%)		46/353 (13%)
Fatigue	46/349 (13.2%)		51/353 (14.4%)
Oedema peripheral	27/349 (7.7%)		45/353 (12.7%)
Pyrexia	41/349 (11.7%)		29/353 (8.2%)
Chills	17/349 (4.9%)		18/353 (5.1%)
Infections and infestations
Respiratory tract infection viral	23/349 (6.6%)		13/353 (3.7%)
Upper respiratory tract infection	36/349 (10.3%)		46/353 (13%)
Nasopharyngitis	21/349 (6%)		19/353 (5.4%)
Urinary tract infection	5/349 (1.4%)		19/353 (5.4%)
Injury, poisoning and procedural complications
Infusion related reaction	33/349 (9.5%)		31/353 (8.8%)
Investigations
Alanine aminotransferase increased	42/349 (12%)		45/353 (12.7%)
Aspartate aminotransferase increased	36/349 (10.3%)		31/353 (8.8%)
Blood alkaline phosphatase increased	28/349 (8%)		26/353 (7.4%)
Ejection fraction decreased	49/349 (14%)		45/353 (12.7%)
Weight increased	20/349 (5.7%)		22/353 (6.2%)
Metabolism and nutrition disorders
Decreased appetite	23/349 (6.6%)		21/353 (5.9%)
Musculoskeletal and connective tissue disorders
Arthralgia	44/349 (12.6%)		38/353 (10.8%)
Back pain	18/349 (5.2%)		33/353 (9.3%)
Bone pain	20/349 (5.7%)		14/353 (4%)
Myalgia	26/349 (7.4%)		35/353 (9.9%)
Pain in extremity	22/349 (6.3%)		24/353 (6.8%)
Nervous system disorders
Dizziness	38/349 (10.9%)		30/353 (8.5%)
Headache	53/349 (15.2%)		73/353 (20.7%)
Neuropathy peripheral	33/349 (9.5%)		34/353 (9.6%)
Peripheral sensory neuropathy	93/349 (26.6%)		85/353 (24.1%)
Respiratory, thoracic and mediastinal disorders
Cough	33/349 (9.5%)		32/353 (9.1%)
Dyspnoea	20/349 (5.7%)		22/353 (6.2%)
Epistaxis	15/349 (4.3%)		23/353 (6.5%)
Skin and subcutaneous tissue disorders
Alopecia	189/349 (54.2%)		186/353 (52.7%)
Pruritus	12/349 (3.4%)		23/353 (6.5%)
Rash	26/349 (7.4%)		26/353 (7.4%)
Vascular disorders
Hypertension	40/349 (11.5%)		33/353 (9.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.