Phase II Safety and Efficacy Study of Crizotinib in East Asian Patients With ROS1 Positive, ALK Negative Advanced NSCLC

• Sponsor: Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01945021
• Collaborator: OxOnc Development LP (Other)
• Enrollment: 129
• Locations: 44
• Arm: 1
• Actual Duration (Months): 75.7
• Patients Per Site: 2.9
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

To assess treatment effectiveness and safety of oral crizotinib administered to East Asian patients with Advanced Non-Small Cell Lung Cancer (NSCLC) that is confirmed to be positive for a ROS1 positive gene mutation (translocation or inversion) and confirmed negative for an ALK mutation

Condition or Disease	Intervention/Treatment	Phase
Non Small Cell Lung Cancer; ROS1 Proto Oncogene; Crizotinib	Drug: Crizotinib	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 129 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II, Open Label, Single Arm Study of the Efficacy and Safety of Crizotinib in East Asian Patients With Advanced ALK-Negative NSCLC Harboring a Translocation or Inversion Involving the c-ROS Oncogene (ROS1) Locus
• Actual Study Start Date: Sep 30, 2013
• Actual Primary Completion Date: Jul 31, 2015
• Actual Study Completion Date: Jan 22, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Crizotinib Single-arm trial whereby all consented, enrolled, eligible patients receive crizotinib	Drug: Crizotinib; Other Names: Xalkori

Outcome Measures

Primary Outcome Measures

1. Independent Radiology Reviewed Overall Objective Response (ORR) [Starting from the first dose study treatment until the first documented CR or PR (every 8 weeks then after 8 cycles at every 12 weeks in duration of 94.0 weeks)]

   Overall objective response (ORR) was defined as the number of patients with a best overall response of confirmed Complete Response or confirmed Partial Response according to RECIST v1.1 (as determined by Independent Radiology Review [IRR]), relative to the total population of response-evaluable participants. Per RECIST v1.1, CR: disappearance of all target lesions. Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (<10 mm short axis); PR: at least 30% decrease in sum of diameters of target lesions, taking as reference baseline sum diameters. Confirmed responses were those that persisted on repeat imaging at least 4 weeks after the initial documentation of response.

Secondary Outcome Measures

1. IRR-Assessed Duration of Response (DR) [From first documentation of objective tumor response to first documentation of objective PD or death due to any cause, whichever occurred first (every 8 weeks then after 8 cycles at every 12 weeks in duration of 151.3 weeks)]

   DR: time from first documentation of objective tumor response (CR or PR) to first documentation of objective progressive disease (PD) or to death due to any cause, whichever occurred first. If no progression or death on study was observed, or given antitumor treatment other than study drug, participants were censored on date of last on-study tumor assessment. RECIST v1.1, a) PD: >=20% increase in sum of diameters of target lesions, taking as reference the smallest sum on study (this includes baseline sum if that is the smallest on study), sum must also demonstrate an absolute increase of >=5 mm, appearance of 1 or more new lesions, unequivocal progression of existing non-target lesions; b) CR: disappearance of all target lesions. Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (<10 mm short axis); c) PR: >=30% decrease in sum of diameters of target lesions, taking as reference baseline sum diameters.

2. IRR-Assessed Time to Tumor Response (TTR) [From date of first dose of crizotinib to first documentation of objective response was observed (every 8 weeks then after 8 cycles at every 12 weeks in duration of 151.3 weeks)]

   TTR was defined as the time from the date of first dose to first documentation of objective tumor response (CR or PR), that was subsequently confirmed. For participants proceeding from PR to CR, the onset of PR was taken as the onset of response. RECIST v1.1 (as determined by IRR), a) CR: disappearance of all target lesions. Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (<10 mm short axis); b) PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

3. IRR Assessed Disease Control Rate (DCR) at 8 Weeks [At 8 weeks after the start of study treatment]

   DCR at 8 weeks was defined as the percentage of participants with a confirmed CR, confirmed PR, or stable disease (SD) at 8 weeks, respectively, relative to the total population of response evaluable participants. RECIST v1.1 (as determined by IRR), a) CR: disappearance of all target lesions. Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (<10 mm short axis); b) PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.

4. IRR-Assessed Progression Free Survival (PFS) [From the date of first dose of crizotinib until the first documentation of objective PD or death (every 8 weeks then after 8 cycles at every 12 weeks in duration of 151.3 weeks)]

   PFS was defined as the time from the date of the first dose of crizotinib to first documentation of objective PD or to death on study due to any cause, whichever occurred first. If no progression or death on study was observed, or given antitumor treatment other than study drug, participants were censored on date of last on-study tumor assessment. RECIST v1.1, PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered a sign of progression. Unequivocal progression of existing non-target lesions.

5. Overall Survival (OS) [From date of the first dose of crizotinib until the date of death from any cause (up to 291.9 weeks)]

   OS was defined as the time from the date of the first dose of crizotinib to the date of death due to any cause. For participants still alive at the time of analysis, the OS time was censored on the last date the participants were known to be alive.

6. Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious AEs, Treatment Emergent Treatment Related AEs and SAEs, Grade 3 or 4 Treatment Emergent AEs and Grade 3 or 4 Treatment Emergent Treatment Related AEs [Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks)]

   Treatment-emergent AEs :between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. Relatedness to crizotinib was assessed by the investigator. Treatment-related AE: any untoward medical occurrence attributed to study drug in a participant who received study drug. Serious adverse event (SAE):an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Grade 3 (Severe) events=unacceptable or intolerable events, significantly interrupting usual daily activity, require systemic drug therapy/other treatment. Grade 4 (Life-threatening) events caused participant to be in imminent danger of death.

7. Number of Participants With a Shift in Hematology Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 [Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks)]

   Laboratory values included hemoglobin increased, anemia, platelet count decreased, leukocytosis, white blood cell decreased, lymphocyte count increased, lymphocyte count decreased and neutrophil count decreased. Laboratory values were defined as National Cancer Institute Common Toxicity Criteria for Adverse Events Version 3.0 (NCI CTCAE v3.0) grade 3 or higher.

8. Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 [Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks)]

   Laboratory values included blood bilirubin increased, alanine aminotransferase increased, aspartate aminotransferase increased, alkaline phosphatase increased, hypoalbuminemia, hypernatremia, hyponatremia, hyperkalemia, hypokalemia, hypercalcemia, hypocalcemia, hypophosphatemia, Creatinine increased, hyperuricemia, hypermagnesemia, hypomagnesemia, hyperglycemia and hypoglycemia. Laboratory values were defined as National Cancer Institute Common Toxicity Criteria for Adverse Events Version 3.0 (NCI CTCAE v3.0) grade 3 or higher.

9. Change From Baseline to Cycle 60 in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QOL) Questionnaire Core 30 (QLQ-C30) Scores [Baseline up to Cycle 60]

   The EORTC QLQ-C30 consists of 30 questions which are incorporated into 5 functional domains (physical, role, cognitive, emotional, and social); a global health status/global QOL scale; 3 symptom scales (fatigue, pain, nausea and vomiting scales); and 6 single items that assess the additional symptoms (dyspnea, appetite loss, sleep disturbance/insomnia, constipation, and diarrhea) and the perceived financial burden of treatment. All the scales and single-item scores ranged from 0 to 100, higher score is indicative of a higher response level (high score for a functional scale represents a high / healthy level of functioning; high score for the global health status / QoL represents a high QoL; a high score for a symptom scale / item represents a high level of symptomatology / problems).

10. Change From Baseline to Cycle 60 in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Lung Cancer Module 13 Scores [Baseline up to Cycle 60]

    The EORTC QLQ-LC13 consisted of 1 multi-item scale and 9 single items that assessed specific symptoms (dyspnea, cough, hemoptysis, and site-specific pain), side effects (sore mouth, dysphagia, neuropathy, and alopecia). Scores on each scale and item ranged from 0 to 100, higher score is indicative of a higher response level (a high score for a symptom scale / item represents a high level of symptomatology / problems).

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Histologically or cytologically proven diagnosis of NSCLC that is locally advanced or metastatic

• treatment-naïve or have received no more than 3 systemic treatment regimen(s)

• Positive for translocation or inversion events involving the ROS1 gene

• Negative for translocation or inversion events involving the ALK gene

• Patients with brain metastases are eligible if asymptomatic, or if treated, must be neurologically stable for at least 2 weeks and are not taking any contraindicated medications

• Any prior treatment (chemotherapy, radiation [except for palliative], or surgery) must have been completed at least 2 weeks prior to initiation of study medication

• At least 1 measurable tumor lesion as per RECIST v1.1

• Female or male, 18 years of age or older

• ECOG performance status 0 to 1

• Adequate organ function

• Signed and dated informed consent

• Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures, including completion of the PRO measures

• Agree to use effective contraception during the study period and for at least 90 days after completion of the study treatment

Exclusion Criteria:

• Current treatment on another therapeutic clinical trial

• Prior therapy specifically directed against ALK or ROS1 fusion genes

• Spinal cord compression unless treated with the patient attaining good pain control and stable or recovered neurologic function, carcinomatous meningitis, or leptomeningeal disease

• known interstitial fibrosis or interstitial lung disease

• myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, congestive heart failure, or cerebrovascular accident including transient ischemic attack within 3 months prior to start of study treatment

• Ongoing cardiac dysrhythmias of NCI CTCAE v4.03 Grade >/=2, uncontrolled atrial fibrillation of any grade, or QTc >470 msec

• Pregnant or breast feeding

• Use of drugs or foods that are known potent CYP3A4 inhibitors or inducers

• Use of other anti-cancer drugs including traditional Chinese medicine on the SFDA list

• Evidence of active malignancy within last 3 years

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The First Affiliated Hospital of Anhui Medical University, Department of Medical Oncology	Hefei	Anhui	China	230022
2	Department of Medical Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences	Chaoyang District	Beijing	China	100021
3	The Military General Hospital of Beijing PLA / Medical Oncology Dept.	Dongcheng District	Beijing	China	100700
4	307 Hospital of PLA/Department of Lung Cancer	Fengtai District	Beijing	China	100071
5	Beijing Cancer Hospital, Department of Thoracic Oncology	Haidian District	Beijing	China	100142
6	Chinese PLA General Hospital	Haidian District	Beijing	China	100853
7	Beijing Chest Hospital	Tongzhou District	Beijing	China
8	Respiration department,the First Affiliated Hospital of Third Military Medical University, PLA	Shapingba District	Chongqing	China	400038
9	Fujian Province Oncology Hospital	Fuzhou	Fujian	China	350014
10	SUN Yat-Sen University Cancer Center	Guangzhou	Guangdong	China	510060
11	The First Affiliated Hospital of Guangzhou Medical College	Guangzhou	Guangdong	China	510120
12	Guangdong General Hospital	Guangzhou	Guangdong	China
13	Hunan Provincial Tumor Hospital/Division of Oncology	Changsha	Hunan	China	410013
14	Department of Oncology, Jilin Provincial Cancer Hospital	Changchun	Jilin	China
15	The affiliated hospital of medical college Qingdao University / Medical oncology department	Qingdao	Shandong	China	266101
16	Department of Pulmonary Medicine, Shanghai Chest Hospital	Shanghai	Shanghai	China	200030
17	Shanghai Chest Hospital/Lung cancer clinical center	Shanghai	Shanghai	China	200030
18	Shanghai Pulmonary Hospital	Shanghai	Shanghai	China	200433
19	Zhongshan Hospital Fudan University / Respiratory Department	Xuhui District	Shanghai	China	200032
20	Oncology Department, West China Hospital of Sichuan University	Chengdu	Sichuan	China	610041
21	Sichuan Province Cancer Hospital/Department of Pulmonary Tumor	Chengdu	Sichuan	China	610041
22	Department of Thoracic Oncology, Tianjin Medical University Cancer Institute and Hospital	Hexi District	Tianjin	China	300060
23	The First Affiliated Hospital of College of Medicine, Zhejiang University	Hangzhou	Zhejiang	China	310003
24	Sir Run Run Shaw Hospital of College of Medicine of Zhejiang University, Center for Oncology	Hangzhou	Zhejiang	China	310016
25	Zhejiang Cancer Hospital	Hangzhou	Zhejiang	China
26	Shizuoka Cancer Center	Sunto-gun	Shizuoka	Japan	411-8777
27	Aichi Cancer Center Hospital	Aichi		Japan
28	National Cancer Center Hospital East	Chiba		Japan
29	NHO Shikoku Cancer Center	Ehime		Japan
30	NHO Kyushu Cancer Center	Fukuoka		Japan
31	Hyogo Cancer Center	Hyogo		Japan
32	Tohoku University Hospital	Miyagi		Japan
33	Kinki University Hospital	Osaka		Japan
34	Osaka City General Hospital	Osaka		Japan
35	Cancer Institute Hospital of JFCR	Tokyo		Japan
36	National Cancer Center Hospital	Tokyo		Japan
37	Asan Medical Center	Seoul		Korea, Republic of
38	Samsung Medical Center	Seoul		Korea, Republic of
39	Seoul National University Hospital	Seoul		Korea, Republic of
40	Yonsei University, Severance Hospital	Seoul		Korea, Republic of
41	Taichung Veterans General Hospital	Taichung		Taiwan
42	National Cheng Kung University Hospital	Tainan		Taiwan
43	National Taiwan University Hospital	Taipei		Taiwan
44	Taipei Veterans General Hospital	Taipei		Taiwan

Sponsors and Collaborators

• Pfizer
• OxOnc Development LP

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT01945021
• Other Study ID Numbers: OO 12-01
• First Posted: Sep 18, 2013
• Last Update Posted: Feb 21, 2021
• Last Verified: Feb 1, 2021

• Keywords provided by Pfizer: Non small cell lung cancer; NSCLC; ROS1; ROS1 positive; ROS1 proto oncogene; c ros tyrosine kinases; ROS1 positive NSCLC; ROS1 lung cancer; ALK negative; Lung Carcinoma; Neoplasm; Crizotinib; Xalkori; Previously treated or untreated; North East Asian
• Additional relevant MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Crizotinib

Study Results

Participant Flow

Pre-assignment Detail	129 participants with anaplastic lymphoma kinase (ALK) negative advanced non-small cell lung cancer (NSCLC) harboring a translocation or inversion event involving the c-ros oncogene 1 (ROS1) locus were enrolled of whom 127 were allocated to treatment with crizotinib and 2 participants had screen failures.

Arm/Group Title	Crizotinib 250 mg
Arm/Group Description	Participants received crizotinib 250 mg orally twice a day in a cycle of 28 days. Dose was modified by investigator if there was treatment-related toxicity. Maximum treatment exposure time was of 291.9 weeks up to final analysis date.
Period Title: Overall Study
STARTED	127
Safety Population	127
Response Evaluable Population	127
Patient Reported Outcome Evaluable	123
COMPLETED	44
NOT COMPLETED	83

Baseline Characteristics

Arm/Group Title	Crizotinib 250 mg
Arm/Group Description	Participants received crizotinib 250 mg orally twice a day in a cycle of 28 days. Dose was modified by investigator if there was treatment-related toxicity. Maximum treatment exposure time was of 291.9 weeks up to final analysis date.
Overall Participants	127
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	52.48 (12.136)
Sex: Female, Male (Count of Participants)
Female	73 57.5%
Male	54 42.5%
Race/Ethnicity, Customized (Count of Participants)
Asian	127 100%
Region of Enrollment (Count of Participants)
China	74 58.3%
Japan	26 20.5%
Korea	12 9.4%
Taiwan	15 11.8%

Outcome Measures

1. Primary Outcome

Title	Independent Radiology Reviewed Overall Objective Response (ORR)
Description	Overall objective response (ORR) was defined as the number of patients with a best overall response of confirmed Complete Response or confirmed Partial Response according to RECIST v1.1 (as determined by Independent Radiology Review [IRR]), relative to the total population of response-evaluable participants. Per RECIST v1.1, CR: disappearance of all target lesions. Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (<10 mm short axis); PR: at least 30% decrease in sum of diameters of target lesions, taking as reference baseline sum diameters. Confirmed responses were those that persisted on repeat imaging at least 4 weeks after the initial documentation of response.
Time Frame	Starting from the first dose study treatment until the first documented CR or PR (every 8 weeks then after 8 cycles at every 12 weeks in duration of 94.0 weeks)

Outcome Measure Data

Analysis Population Description

The response-evaluable population (RES) population included all enrolled participants who received at least 1 dose of study medication and had an adequate baseline tumor assessment.

Arm/Group Title	Crizotinib 250 mg
Arm/Group Description	Participants received crizotinib 250 mg orally twice a day in a cycle of 28 days. Dose was modified by investigator if there was treatment-related toxicity. Maximum treatment exposure time was of 291.9 weeks up to final analysis date.
Measure Participants	127
Count of Participants [Participants]	88 69.3%

2. Secondary Outcome

Title	IRR-Assessed Duration of Response (DR)
Description	DR: time from first documentation of objective tumor response (CR or PR) to first documentation of objective progressive disease (PD) or to death due to any cause, whichever occurred first. If no progression or death on study was observed, or given antitumor treatment other than study drug, participants were censored on date of last on-study tumor assessment. RECIST v1.1, a) PD: >=20% increase in sum of diameters of target lesions, taking as reference the smallest sum on study (this includes baseline sum if that is the smallest on study), sum must also demonstrate an absolute increase of >=5 mm, appearance of 1 or more new lesions, unequivocal progression of existing non-target lesions; b) CR: disappearance of all target lesions. Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (<10 mm short axis); c) PR: >=30% decrease in sum of diameters of target lesions, taking as reference baseline sum diameters.
Time Frame	From first documentation of objective tumor response to first documentation of objective PD or death due to any cause, whichever occurred first (every 8 weeks then after 8 cycles at every 12 weeks in duration of 151.3 weeks)

Outcome Measure Data

Analysis Population Description

The RES population included all enrolled participants who received at least 1 dose of study medication and had an adequate baseline tumor assessment. Here, "Overall Number of Participants Analyzed" signifies number of participants with a confirmed objective response that could have occurred anytime up to 151.3 weeks.

Arm/Group Title	Crizotinib 250 mg
Arm/Group Description	Participants received crizotinib 250 mg orally twice a day in a cycle of 28 days. Dose was modified by investigator if there was treatment-related toxicity. Maximum treatment exposure time was of 291.9 weeks up to final analysis date.
Measure Participants	91
Median (95% Confidence Interval) [Months]	19.7

3. Secondary Outcome

Title	IRR-Assessed Time to Tumor Response (TTR)
Description	TTR was defined as the time from the date of first dose to first documentation of objective tumor response (CR or PR), that was subsequently confirmed. For participants proceeding from PR to CR, the onset of PR was taken as the onset of response. RECIST v1.1 (as determined by IRR), a) CR: disappearance of all target lesions. Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (<10 mm short axis); b) PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time Frame	From date of first dose of crizotinib to first documentation of objective response was observed (every 8 weeks then after 8 cycles at every 12 weeks in duration of 151.3 weeks)

Outcome Measure Data

Analysis Population Description

The RES population included all enrolled participants who received at least 1 dose of study medication and had an adequate baseline tumor assessment. Here, "Overall Number of Participants Analyzed" signifies number of participants with a confirmed objective response that could have occurred anytime up to 151.3 weeks.

Arm/Group Title	Crizotinib 250 mg
Arm/Group Description	Participants received crizotinib 250 mg orally twice a day in a cycle of 28 days. Dose was modified by investigator if there was treatment-related toxicity. Maximum treatment exposure time was of 291.9 weeks up to final analysis date.
Measure Participants	91
Median (Full Range) [Months]	1.9

4. Secondary Outcome

Title	IRR Assessed Disease Control Rate (DCR) at 8 Weeks
Description	DCR at 8 weeks was defined as the percentage of participants with a confirmed CR, confirmed PR, or stable disease (SD) at 8 weeks, respectively, relative to the total population of response evaluable participants. RECIST v1.1 (as determined by IRR), a) CR: disappearance of all target lesions. Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (<10 mm short axis); b) PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
Time Frame	At 8 weeks after the start of study treatment

Outcome Measure Data

Analysis Population Description

The RES population included all enrolled participants who received at least 1 dose of study medication and had an adequate baseline tumor assessment.

Arm/Group Title	Crizotinib 250 mg
Arm/Group Description	Participants received crizotinib 250 mg orally twice a day in a cycle of 28 days. Dose was modified by investigator if there was treatment-related toxicity. Maximum treatment exposure time was of 291.9 weeks up to final analysis date.
Measure Participants	127
Number (95% Confidence Interval) [Percentage of participants]	88.2 69.4%

5. Secondary Outcome

Title	IRR-Assessed Progression Free Survival (PFS)
Description	PFS was defined as the time from the date of the first dose of crizotinib to first documentation of objective PD or to death on study due to any cause, whichever occurred first. If no progression or death on study was observed, or given antitumor treatment other than study drug, participants were censored on date of last on-study tumor assessment. RECIST v1.1, PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered a sign of progression. Unequivocal progression of existing non-target lesions.
Time Frame	From the date of first dose of crizotinib until the first documentation of objective PD or death (every 8 weeks then after 8 cycles at every 12 weeks in duration of 151.3 weeks)

Outcome Measure Data

Analysis Population Description

The safety analysis population (SAF) included all enrolled participants who received at least 1 dose of study medication.

Arm/Group Title	Crizotinib 250 mg
Arm/Group Description	Participants received crizotinib 250 mg orally twice a day in a cycle of 28 days. Dose was modified by investigator if there was treatment-related toxicity. Maximum treatment exposure time was of 291.9 weeks up to final analysis date.
Measure Participants	127
Median (95% Confidence Interval) [Months]	15.9

6. Secondary Outcome

Title	Overall Survival (OS)
Description	OS was defined as the time from the date of the first dose of crizotinib to the date of death due to any cause. For participants still alive at the time of analysis, the OS time was censored on the last date the participants were known to be alive.
Time Frame	From date of the first dose of crizotinib until the date of death from any cause (up to 291.9 weeks)

Outcome Measure Data

Analysis Population Description

SAF included all enrolled participants who received at least 1 dose of study medication.

Arm/Group Title	Crizotinib 250 mg
Arm/Group Description	Participants received crizotinib 250 mg orally twice a day in a cycle of 28 days. Dose was modified by investigator if there was treatment-related toxicity. Maximum treatment exposure time was of 291.9 weeks up to final analysis date.
Measure Participants	127
Median (95% Confidence Interval) [Months]	44.2

7. Secondary Outcome

Title	Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious AEs, Treatment Emergent Treatment Related AEs and SAEs, Grade 3 or 4 Treatment Emergent AEs and Grade 3 or 4 Treatment Emergent Treatment Related AEs
Description	Treatment-emergent AEs :between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. Relatedness to crizotinib was assessed by the investigator. Treatment-related AE: any untoward medical occurrence attributed to study drug in a participant who received study drug. Serious adverse event (SAE):an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Grade 3 (Severe) events=unacceptable or intolerable events, significantly interrupting usual daily activity, require systemic drug therapy/other treatment. Grade 4 (Life-threatening) events caused participant to be in imminent danger of death.
Time Frame	Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks)

Outcome Measure Data

Analysis Population Description

SAF included all enrolled participants who received at least 1 dose of study medication.

Arm/Group Title	Crizotinib 250 mg
Arm/Group Description	Participants received crizotinib 250 mg orally twice a day in a cycle of 28 days. Dose was modified by investigator if there was treatment-related toxicity. Maximum treatment exposure time was of 291.9 weeks up to final analysis date.
Measure Participants	127
Incidence of All-Causality Adverse Events	127 100%
Incidence of All-Causality Serious Adverse Events	46 36.2%
Incidence of Treatment Related Adverse Events	124 97.6%
Incidence of Treatment Related Serious Adverse Events	11 8.7%
Incidence of All-Causality Grade 3-4 Adverse Event	68 53.5%
Incidence of Treatment Related Grade 3-4 Adverse Event	41 32.3%

8. Secondary Outcome

Title	Number of Participants With a Shift in Hematology Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4
Description	Laboratory values included hemoglobin increased, anemia, platelet count decreased, leukocytosis, white blood cell decreased, lymphocyte count increased, lymphocyte count decreased and neutrophil count decreased. Laboratory values were defined as National Cancer Institute Common Toxicity Criteria for Adverse Events Version 3.0 (NCI CTCAE v3.0) grade 3 or higher.
Time Frame	Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks)

Outcome Measure Data

Analysis Population Description

SAF included all enrolled participants who received at least 1 dose of study medication. Here, "number analyzed" signifies participants evaluable at specific rows.

Arm/Group Title	Crizotinib 250 mg
Arm/Group Description	Participants received crizotinib 250 mg orally twice a day in a cycle of 28 days. Dose was modified by investigator if there was treatment-related toxicity. Maximum treatment exposure time was of 291.9 weeks up to final analysis date.
Measure Participants	127
Hemoglobin Increased: Baseline Grade 0 to Worst Grade 3	0 0%
Hemoglobin Increased: Baseline Grade 1 to Worst Grade 3	0 0%
Hemoglobin Increased: Baseline Grade 2 to Worst Grade 3	0 0%
Anemia: Baseline Grade 0 to Worst Grade 3	2 1.6%
Anemia: Baseline Grade 1 to Worst Grade 3	1 0.8%
Anemia: Baseline Grade 2 to Worst Grade 3	5 3.9%
Anemia: Baseline Grade 0 to Worst Grade 4	0 0%
Anemia: Baseline Grade 1 to Worst Grade 4	0 0%
Anemia: Baseline Grade 2 to Worst Grade 4	0 0%
Platelet Count Decreased: Baseline Grade 0 to Worst Grade 3	0 0%
Platelet Count Decreased: Baseline Grade 1 to Worst Grade 3	0 0%
Platelet Count Decreased: Baseline Grade 2 to Worst Grade 3	0 0%
Platelet Count Decreased: Baseline Grade 0 to Worst Grade 4	0 0%
Platelet Count Decreased: Baseline Grade 1 to Worst Grade 4	0 0%
Platelet Count Decreased: Baseline Grade 2 to Worst Grade 4	0 0%
Leukocytosis: Baseline Grade 0 to Worst Grade 3	0 0%
Leukocytosis: Baseline Grade 0 to Worst Grade 4	0 0%
White Blood Cell Decreased: Baseline Grade 0 to Worst Grade 3	3 2.4%
White Blood Cell Decreased: Baseline Grade 1 to Worst Grade 3	1 0.8%
White Blood Cell Decreased: Baseline Grade 2 to Worst Grade 3	0 0%
White Blood Cell Decreased: Baseline Grade 0 to Worst Grade 4	0 0%
White Blood Cell Decreased: Baseline Grade 1 to Worst Grade 4	0 0%
White Blood Cell Decreased: Baseline Grade 2 to Worst Grade 4	0 0%
Lymphocyte Count Increased: Baseline Grade 0 to Worst Grade 3	0 0%
Lymphocyte Count Increased: Baseline Grade 2 to Worst Grade 3	0 0%
Lymphocyte Count Decreased: Baseline Grade 0 to Worst Grade 3	4 3.1%
Lymphocyte Count Decreased: Baseline Grade 1 to Worst Grade 3	0 0%
Lymphocyte Count Decreased: Baseline Grade 2 to Worst Grade 3	2 1.6%
Lymphocyte Count Decreased: Baseline Grade 0 to Worst Grade 4	0 0%
Lymphocyte Count Decreased: Baseline Grade 1 to Worst Grade 4	0 0%
Lymphocyte Count Decreased: Baseline Grade 2 to Worst Grade 4	0 0%
Neutrophil Count Decreased: Baseline Grade 0 to Worst Grade 3	7 5.5%
Neutrophil Count Decreased: Baseline Grade 1 to Worst Grade 3	1 0.8%
Neutrophil Count Decreased: Baseline Grade 2 to Worst Grade 3	0 0%
Neutrophil Count Decreased: Baseline Grade 0 to Worst Grade 4	4 3.1%
Neutrophil Count Decreased: Baseline Grade 1 to Worst Grade 4	0 0%
Neutrophil Count Decreased: Baseline Grade 2 to Worst Grade 4	0 0%

9. Secondary Outcome

Title	Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4
Description	Laboratory values included blood bilirubin increased, alanine aminotransferase increased, aspartate aminotransferase increased, alkaline phosphatase increased, hypoalbuminemia, hypernatremia, hyponatremia, hyperkalemia, hypokalemia, hypercalcemia, hypocalcemia, hypophosphatemia, Creatinine increased, hyperuricemia, hypermagnesemia, hypomagnesemia, hyperglycemia and hypoglycemia. Laboratory values were defined as National Cancer Institute Common Toxicity Criteria for Adverse Events Version 3.0 (NCI CTCAE v3.0) grade 3 or higher.
Time Frame	Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks)

Outcome Measure Data

Analysis Population Description

SAF included all enrolled participants who received at least one dose of study medication. Here, "number analyzed" signifies participants evaluable at specific rows.

Arm/Group Title	Crizotinib 250 mg
Arm/Group Description	Participants received crizotinib 250 mg orally twice a day in a cycle of 28 days. Dose was modified by investigator if there was treatment-related toxicity. Maximum treatment exposure time was of 291.9 weeks up to final analysis date.
Measure Participants	127
Blood Bilirubin Increased: Baseline Grade 0 to Worst Grade 3	1 0.8%
Blood Bilirubin Increased: Baseline Grade 1 to Worst Grade 3	0 0%
Blood Bilirubin Increased: Baseline Grade 2 to Worst Grade 3	0 0%
Blood Bilirubin Increased: Baseline Grade 0 to Worst Grade 4	0 0%
Blood Bilirubin Increased: Baseline Grade 1 to Worst Grade 4	0 0%
Blood Bilirubin Increased: Baseline Grade 2 to Worst Grade 4	0 0%
Alanine Aminotransferase Increased: Baseline Grade 0 to Worst Grade 3	4 3.1%
Alanine Aminotransferase Increased: Baseline Grade 1 to Worst Grade 3	1 0.8%
Alanine Aminotransferase Increased: Baseline Grade 2 to Worst Grade 3	0 0%
Alanine Aminotransferase Increased: Baseline Grade 0 to Worst Grade 4	4 3.1%
Alanine Aminotransferase Increased: Baseline Grade 1 to Worst Grade 4	0 0%
Alanine Aminotransferase Increased: Baseline Grade 2 to Worst Grade 4	0 0%
Aspartate Aminotransferase Increased : Baseline Grade 0 to Worst Grade 3	2 1.6%
Aspartate Aminotransferase Increased : Baseline Grade 1 to Worst Grade 3	0 0%
Aspartate Aminotransferase Increased : Baseline Grade 2 to Worst Grade 3	0 0%
Aspartate Aminotransferase Increased : Baseline Grade 0 to Worst Grade 4	4 3.1%
Aspartate Aminotransferase Increased : Baseline Grade 1 to Worst Grade 4	0 0%
Aspartate Aminotransferase Increased : Baseline Grade 2 to Worst Grade 4	0 0%
Alkaline Phosphatase Increased : Baseline Grade 0 to Worst Grade 3	0 0%
Alkaline Phosphatase Increased : Baseline Grade 1 to Worst Grade 3	0 0%
Alkaline Phosphatase Increased : Baseline Grade 2 to Worst Grade 3	0 0%
Alkaline Phosphatase Increased : Baseline Grade 0 to Worst Grade 4	0 0%
Alkaline Phosphatase Increased : Baseline Grade 1 to Worst Grade 4	0 0%
Alkaline Phosphatase Increased : Baseline Grade 2 to Worst Grade 4	0 0%
Hypoalbuminemia: Baseline Grade 0 to Worst Grade 3	1 0.8%
Hypoalbuminemia: Baseline Grade 1 to Worst Grade 3	1 0.8%
Hypoalbuminemia: Baseline Grade 2 to Worst Grade 3	1 0.8%
Hypoalbuminemia: Baseline Grade 0 to Worst Grade 4	0 0%
Hypoalbuminemia: Baseline Grade 1 to Worst Grade 4	0 0%
Hypoalbuminemia: Baseline Grade 2 to Worst Grade 4	0 0%
Hypernatremia: Baseline Grade 0 to Worst Grade 3	0 0%
Hypernatremia: Baseline Grade 1 to Worst Grade 3	0 0%
Hypernatremia: Baseline Grade 2 to Worst Grade 3	0 0%
Hypernatremia: Baseline Grade 0 to Worst Grade 4	0 0%
Hypernatremia: Baseline Grade 1 to Worst Grade 4	0 0%
Hypernatremia: Baseline Grade 2 to Worst Grade 4	0 0%
Hyponatremia: Baseline Grade 0 to Worst Grade 3	8 6.3%
Hyponatremia: Baseline Grade 1 to Worst Grade 3	4 3.1%
Hyponatremia: Baseline Grade 0 to Worst Grade 4	0 0%
Hyponatremia: Baseline Grade 1 to Worst Grade 4	0 0%
Hyperkalemia: Baseline Grade 0 to Worst Grade 3	0 0%
Hyperkalemia: Baseline Grade 1 to Worst Grade 3	1 0.8%
Hyperkalemia: Baseline Grade 2 to Worst Grade 3	0 0%
Hyperkalemia: Baseline Grade 0 to Worst Grade 4	0 0%
Hyperkalemia: Baseline Grade 1 to Worst Grade 4	0 0%
Hyperkalemia: Baseline Grade 2 to Worst Grade 4	0 0%
Hypokalemia: Baseline Grade 0 to Worst Grade 3	5 3.9%
Hypokalemia: Baseline Grade 1 to Worst Grade 3	0 0%
Hypokalemia: Baseline Grade 2 to Worst Grade 3	0 0%
Hypokalemia: Baseline Grade 0 to Worst Grade 4	1 0.8%
Hypokalemia: Baseline Grade 1 to Worst Grade 4	0 0%
Hypokalemia: Baseline Grade 2 to Worst Grade 4	0 0%
Hypercalcemia: Baseline Grade 0 to Worst Grade 3	0 0%
Hypercalcemia: Baseline Grade 1 to Worst Grade 3	0 0%
Hypercalcemia: Baseline Grade 2 to Worst Grade 3	0 0%
Hypercalcemia: Baseline Grade 0 to Worst Grade 4	0 0%
Hypercalcemia: Baseline Grade 1 to Worst Grade 4	0 0%
Hypercalcemia: Baseline Grade 2 to Worst Grade 4	0 0%
Hypocalcemia: Baseline Grade 0 to Worst Grade 3	0 0%
Hypocalcemia: Baseline Grade 1 to Worst Grade 3	0 0%
Hypocalcemia: Baseline Grade 2 to Worst Grade 3	0 0%
Hypocalcemia: Baseline Grade 0 to Worst Grade 4	0 0%
Hypocalcemia: Baseline Grade 1 to Worst Grade 4	0 0%
Hypocalcemia: Baseline Grade 2 to Worst Grade 4	0 0%
Hypophosphatemia: Baseline Grade 0 to Worst Grade 3	11 8.7%
Hypophosphatemia: Baseline Grade 1 to Worst Grade 3	0 0%
Hypophosphatemia: Baseline Grade 2 to Worst Grade 3	1 0.8%
Hypophosphatemia: Baseline Grade 0 to Worst Grade 4	1 0.8%
Hypophosphatemia: Baseline Grade 1 to Worst Grade 4	0 0%
Hypophosphatemia: Baseline Grade 2 to Worst Grade 4	0 0%
Creatinine Increased: Baseline Grade 0 to Worst Grade 3	1 0.8%
Creatinine Increased: Baseline Grade 1 to Worst Grade 3	0 0%
Creatinine Increased: Baseline Grade 2 to Worst Grade 3	0 0%
Creatinine Increased: Baseline Grade 0 to Worst Grade 4	0 0%
Creatinine Increased: Baseline Grade 1 to Worst Grade 4	0 0%
Creatinine Increased: Baseline Grade 2 to Worst Grade 4	0 0%
Hyperuricemia: Baseline Grade 0 to Worst Grade 3	33 26%
Hyperuricemia: Baseline Grade 1 to Worst Grade 3	0 0%
Hyperuricemia: Baseline Grade 0 to Worst Grade 4	0 0%
Hyperuricemia: Baseline Grade 1 to Worst Grade 4	0 0%
Hypermagnesemia: Baseline Grade 0 to Worst Grade 3	2 1.6%
Hypermagnesemia: Baseline Grade 1 to Worst Grade 3	0 0%
Hypermagnesemia: Baseline Grade 0 to Worst Grade 4	0 0%
Hypermagnesemia: Baseline Grade 1 to Worst Grade 4	0 0%
Hypomagnesemia: Baseline Grade 0 to Worst Grade 3	0 0%
Hypomagnesemia: Baseline Grade 1 to Worst Grade 3	0 0%
Hypomagnesemia: Baseline Grade 2 to Worst Grade 3	0 0%
Hypomagnesemia: Baseline Grade 0 to Worst Grade 4	0 0%
Hypomagnesemia: Baseline Grade 1 to Worst Grade 4	0 0%
Hypomagnesemia: Baseline Grade 2 to Worst Grade 4	0 0%
Hyperglycemia: Baseline Grade 0 to Worst Grade 3	1 0.8%
Hyperglycemia: Baseline Grade 1 to Worst Grade 3	1 0.8%
Hyperglycemia: Baseline Grade 2 to Worst Grade 3	0 0%
Hyperglycemia: Baseline Grade 0 to Worst Grade 4	0 0%
Hyperglycemia: Baseline Grade 1 to Worst Grade 4	0 0%
Hyperglycemia: Baseline Grade 2 to Worst Grade 4	0 0%
Hypoglycemia: Baseline Grade 0 to Worst Grade 3	0 0%
Hypoglycemia: Baseline Grade 1 to Worst Grade 3	0 0%
Hypoglycemia: Baseline Grade 2 to Worst Grade 3	0 0%
Hypoglycemia: Baseline Grade 0 to Worst Grade 4	0 0%
Hypoglycemia: Baseline Grade 1 to Worst Grade 4	0 0%
Hypoglycemia: Baseline Grade 2 to Worst Grade 4	0 0%

10. Secondary Outcome

Title	Change From Baseline to Cycle 60 in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QOL) Questionnaire Core 30 (QLQ-C30) Scores
Description	The EORTC QLQ-C30 consists of 30 questions which are incorporated into 5 functional domains (physical, role, cognitive, emotional, and social); a global health status/global QOL scale; 3 symptom scales (fatigue, pain, nausea and vomiting scales); and 6 single items that assess the additional symptoms (dyspnea, appetite loss, sleep disturbance/insomnia, constipation, and diarrhea) and the perceived financial burden of treatment. All the scales and single-item scores ranged from 0 to 100, higher score is indicative of a higher response level (high score for a functional scale represents a high / healthy level of functioning; high score for the global health status / QoL represents a high QoL; a high score for a symptom scale / item represents a high level of symptomatology / problems).
Time Frame	Baseline up to Cycle 60

Outcome Measure Data

Analysis Population Description

Patient reported outcome (PRO)-evaluable population (PRO) included enrolled participants who received at least 1 dose of study medication and completed the assessments at baseline and with at least 1 post-baseline time point. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure.

Arm/Group Title	Crizotinib 250 mg
Arm/Group Description	Participants received crizotinib 250 mg orally twice a day in a cycle of 28 days. Dose was modified by investigator if there was treatment-related toxicity. Maximum treatment exposure time was of 291.9 weeks up to final analysis date.
Measure Participants	26
Global Health Status	11.85 (20.844)
Physical Functioning	3.08 (11.964)
Role Functioning	-0.65 (17.945)
Emotional Functioning	10.77 (18.146)
Cognitive Functioning	3.20 (14.159)
Social Functioning	5.13 (20.961)
Fatigue	-12.30 (20.156)
Nausea and Vomiting	0.64 (14.517)
Pain	-12.18 (16.027)
Dyspnea	-6.41 (21.124)
Insomnia	-11.53 (16.161)
Appetite loss	-14.10 (23.428)
Constipation	10.26 (27.920)
Diarrhoea	1.28 (19.937)
Financial difficulties	-21.80 (28.199)

11. Secondary Outcome

Title	Change From Baseline to Cycle 60 in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Lung Cancer Module 13 Scores
Description	The EORTC QLQ-LC13 consisted of 1 multi-item scale and 9 single items that assessed specific symptoms (dyspnea, cough, hemoptysis, and site-specific pain), side effects (sore mouth, dysphagia, neuropathy, and alopecia). Scores on each scale and item ranged from 0 to 100, higher score is indicative of a higher response level (a high score for a symptom scale / item represents a high level of symptomatology / problems).
Time Frame	Baseline up to Cycle 60

Outcome Measure Data

Analysis Population Description

PRO evaluable population included participants from the safety analysis population who completed the assessments at baseline and at least one post-baseline time point. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure.

Arm/Group Title	Crizotinib 250 mg
Arm/Group Description	Participants received crizotinib 250 mg orally twice a day in a cycle of 28 days. Dose was modified by investigator if there was treatment-related toxicity. Maximum treatment exposure time was of 291.9 weeks up to final analysis date.
Measure Participants	26
Dyspnea	-4.74 (14.791)
Coughing	-12.82 (29.936)
Hemoptysis	-5.12 (12.253)
Sore mouth	-1.28 (14.844)
Dysphagia	0.00 (16.314)
Peripheral neuropathy	3.85 (19.611)
Alopecia	-2.57 (20.910)
Pain in chest	-12.82 (21.236)
Pain in arm or shoulder	-15.37 (23.536)
Pain in other parts	-7.68 (21.718)

Adverse Events

Time Frame	Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks)
Adverse Event Reporting Description	Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Arm/Group Title	Crizotinib 250 mg
Arm/Group Description	Participants received crizotinib 250 mg orally twice a day in a cycle of 28 days. Dose was modified by investigator if there was treatment-related toxicity. Maximum treatment exposure time was of 291.9 weeks up to final analysis date.
All Cause Mortality
	Crizotinib 250 mg
	Affected / at Risk (%)	# Events
Total	65/127 (51.2%)
Serious Adverse Events
	Crizotinib 250 mg
	Affected / at Risk (%)	# Events
Total	46/127 (36.2%)
Blood and lymphatic system disorders
Anaemia	1/127 (0.8%)
Cardiac disorders
Acute myocardial infarction	1/127 (0.8%)
Bradycardia	1/127 (0.8%)
Eye disorders
Retinal detachment	1/127 (0.8%)
Gastrointestinal disorders
Abdominal pain	1/127 (0.8%)
Chronic gastritis	1/127 (0.8%)
General disorders
Disease Progression	7/127 (5.5%)
Hernia	1/127 (0.8%)
Peripheral swelling	1/127 (0.8%)
Hepatobiliary disorders
Hepatic cyst	1/127 (0.8%)
Hepatic function abnormal	2/127 (1.6%)
Drug-induced liver injury	1/127 (0.8%)
Liver injury	1/127 (0.8%)
Infections and infestations
Pneumonia	10/127 (7.9%)
Appendicitis	1/127 (0.8%)
Bronchiolitis	1/127 (0.8%)
Bronchopulmonary aspergillosis	1/127 (0.8%)
Cellulitis	1/127 (0.8%)
Empyema	1/127 (0.8%)
Oesophageal infection	1/127 (0.8%)
Urinary tract infection	1/127 (0.8%)
Postoperative wound infection	1/127 (0.8%)
Renal tuberculosis	1/127 (0.8%)
Tuberculosis	1/127 (0.8%)
Injury, poisoning and procedural complications
Road traffic accident	1/127 (0.8%)
Investigations
Alanine aminotransferase increased	2/127 (1.6%)
Aspartate aminotransferase increased	1/127 (0.8%)
Hepatic enzyme increased	1/127 (0.8%)
Metabolism and nutrition disorders
Decreased appetite	1/127 (0.8%)
Malnutrition	1/127 (0.8%)
Hypoproteinaemia	1/127 (0.8%)
Musculoskeletal and connective tissue disorders
Spinal osteoarthritis	1/127 (0.8%)
Arthropathy	1/127 (0.8%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer	1/127 (0.8%)
Colon cancer	1/127 (0.8%)
Lung neoplasm malignant	1/127 (0.8%)
Mediastinum neoplasm	1/127 (0.8%)
Nervous system disorders
Headache	1/127 (0.8%)
Ruptured cerebral aneurysm	1/127 (0.8%)
Seizure	1/127 (0.8%)
Dysarthria	1/127 (0.8%)
Epilepsy	1/127 (0.8%)
Renal and urinary disorders
Renal cyst	2/127 (1.6%)
Chronic kidney disease	1/127 (0.8%)
Respiratory, thoracic and mediastinal disorders
Pleural effusion	3/127 (2.4%)
Respiratory failure	5/127 (3.9%)
Pneumothorax	1/127 (0.8%)
Pulmonary embolism	1/127 (0.8%)
Vascular disorders
Deep vein thrombosis	2/127 (1.6%)
Embolism	1/127 (0.8%)
Other (Not Including Serious) Adverse Events
	Crizotinib 250 mg
	Affected / at Risk (%)	# Events
Total	127/127 (100%)
Blood and lymphatic system disorders
Neutropenia	14/127 (11%)
Anaemia	15/127 (11.8%)
Leukopenia	8/127 (6.3%)
Cardiac disorders
Sinus bradycardia	11/127 (8.7%)
Eye disorders
Vision blurred	25/127 (19.7%)
Visual impairment	22/127 (17.3%)
Diplopia	7/127 (5.5%)
Photopsia	7/127 (5.5%)
Gastrointestinal disorders
Diarrhoea	62/127 (48.8%)
Nausea	58/127 (45.7%)
Vomiting	50/127 (39.4%)
Constipation	49/127 (38.6%)
Abdominal pain upper	12/127 (9.4%)
Abdominal pain	12/127 (9.4%)
Stomatitis	10/127 (7.9%)
Abdominal distension	8/127 (6.3%)
Toothache	10/127 (7.9%)
General disorders
Oedema peripheral	39/127 (30.7%)
Fatigue	22/127 (17.3%)
Pyrexia	23/127 (18.1%)
Chest pain	11/127 (8.7%)
Asthenia	9/127 (7.1%)
Pain	9/127 (7.1%)
Peripheral swelling	9/127 (7.1%)
Hepatobiliary disorders
Hepatic function abnormal	10/127 (7.9%)
Infections and infestations
Nasopharyngitis	28/127 (22%)
Upper respiratory tract infection	22/127 (17.3%)
Pneumonia	11/127 (8.7%)
Urinary tract infection	11/127 (8.7%)
Investigations
Alanine aminotransferase increased	72/127 (56.7%)
Aspartate aminotransferase increased	67/127 (52.8%)
Neutrophil count decreased	37/127 (29.1%)
White blood cell count decreased	30/127 (23.6%)
Blood creatinine increased	29/127 (22.8%)
Gamma-glutamyltransferase increased	18/127 (14.2%)
Blood alkaline phosphate increased	14/127 (11%)
Blood albumin decreased	17/127 (13.4%)
Blood creatine phosphokinase increased	9/127 (7.1%)
Protein total decreased	7/127 (5.5%)
Weight decreased	8/127 (6.3%)
Metabolism and nutrition disorders
Decreased appetite	27/127 (21.3%)
Hypoproteinaemia	14/127 (11%)
Hypoalbuminaemia	18/127 (14.2%)
Hypocalcaemia	10/127 (7.9%)
Hypokalaemia	10/127 (7.9%)
Hyponatraemia	12/127 (9.4%)
Musculoskeletal and connective tissue disorders
Back pain	21/127 (16.5%)
Pain in extremity	16/127 (12.6%)
Arthralgia	10/127 (7.9%)
Musculoskeletal pain	10/127 (7.9%)
Nervous system disorders
Dysgeusia	17/127 (13.4%)
Dizziness	23/127 (18.1%)
Headache	20/127 (15.7%)
Hypoaesthesia	7/127 (5.5%)
Taste disorder	8/127 (6.3%)
Psychiatric disorders
Insomnia	10/127 (7.9%)
Respiratory, thoracic and mediastinal disorders
Cough	35/127 (27.6%)
Dyspnoea	12/127 (9.4%)
Haemoptysis	7/127 (5.5%)
Skin and subcutaneous tissue disorders
Rash	17/127 (13.4%)
Pruritis	11/127 (8.7%)

Limitations/Caveats

Due to small percentage of participants (less than 20%) after Cycle 60, data for EORTC QLQ-C30 score and EORTC QLQ-LC13 score could not be interpreted. 65 participants died during the whole study: 15 participants died within 28 days from last dose of study treatment and were reported as SAEs, while 50 participants died during the survival follow-up.

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.