Trial Outcomes & Findings for A Study of Aflibercept Versus Placebo in Patients With Second-Line Docetaxel for Locally Advanced or Metastatic Non-Small-Cell Lung Cancer (NCT NCT00532155)

Last Updated: 2025-09-10

Results Overview

OS was time interval from the date of randomization to the date of death due to any cause. If death was not observed during the study, overall survival time was censored at the last date the participant was known to be alive, or the study cutoff date, whichever was earlier. The cut-off date for the OS was date when 687 deaths were observed. OS was estimated from Kaplan-Meier Curves.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

913 participants

Primary outcome timeframe

Baseline to the date when 687 deaths occurred (26 January 2011)

Results posted on

2025-09-10

Participant Flow

A total of 1130 participants signed an informed consent to enter the study. Amongst these, 913 were randomized to the two arms in this study. 217 participants were screen failures.

Participant milestones

Participant milestones
Measure	Placebo/Docetaxel Participants with Non-Small-Cell Lung Cancer (NSCLC) were administered Placebo immediately followed by Docetaxel every three weeks until disease progression, unacceptable toxicity, or participant's refusal.	Aflibercept/Docetaxel Participants with Non-Small-Cell Lung Cancer (NSCLC) were administered Aflibercept immediately followed by Docetaxel every three weeks until disease progression, unacceptable toxicity, or participant's refusal.
Overall Study STARTED	457	456
Overall Study SAFETY POPULATION	455	450
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	457	456

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo/Docetaxel Participants with Non-Small-Cell Lung Cancer (NSCLC) were administered Placebo immediately followed by Docetaxel every three weeks until disease progression, unacceptable toxicity, or participant's refusal.	Aflibercept/Docetaxel Participants with Non-Small-Cell Lung Cancer (NSCLC) were administered Aflibercept immediately followed by Docetaxel every three weeks until disease progression, unacceptable toxicity, or participant's refusal.
Overall Study Adverse Event	66	123
Overall Study Lack of Efficacy	332	255
Overall Study Protocol Violation	1	3
Overall Study Lost to Follow-up	2	0
Overall Study Physician Decision	16	15
Overall Study Withdrawal by Subject	23	44
Overall Study Consent withdrawn	5	7
Overall Study Moved	1	0
Overall Study Pre-existing brain metastasis (by MRI)	1	0
Overall Study Occurence of a second cancer	0	1
Overall Study Occurence of a secondary cancer	0	1
Overall Study Promotor ended study	1	0
Overall Study Progressive disease (by incorrect scan)	0	1
Overall Study Had brain metastasis, was mis-randomized	1	0
Overall Study Study stopped	1	0
Overall Study Study terminated by sponsor	1	0
Overall Study Study termination stop further treatment	4	0
Overall Study Did not receive study medication	2	6

Baseline Characteristics

A Study of Aflibercept Versus Placebo in Patients With Second-Line Docetaxel for Locally Advanced or Metastatic Non-Small-Cell Lung Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo/Docetaxel n=457 Participants Participants with Non-Small-Cell Lung Cancer (NSCLC) were administered Placebo immediately followed by Docetaxel every three weeks until disease progression, unacceptable toxicity, or participant's refusal.	Aflibercept/Docetaxel n=456 Participants Participants with Non-Small-Cell Lung Cancer (NSCLC) were administered Aflibercept immediately followed by Docetaxel every three weeks until disease progression, unacceptable toxicity, or participant's refusal.	Total n=913 Participants Total of all reporting groups
Age, Continuous	59.6 Years STANDARD_DEVIATION 9.4 • n=5 Participants	59.6 Years STANDARD_DEVIATION 9.5 • n=7 Participants	59.6 Years STANDARD_DEVIATION 9.4 • n=5 Participants
Age, Customized <65 years	316 participants n=5 Participants	315 participants n=7 Participants	631 participants n=5 Participants
Age, Customized >= and <75 years	122 participants n=5 Participants	121 participants n=7 Participants	243 participants n=5 Participants
Age, Customized >=75 years	19 participants n=5 Participants	20 participants n=7 Participants	39 participants n=5 Participants
Sex/Gender, Customized Male	300 participants n=5 Participants	305 participants n=7 Participants	605 participants n=5 Participants
Sex/Gender, Customized Female	157 participants n=5 Participants	151 participants n=7 Participants	308 participants n=5 Participants
Race/Ethnicity, Customized Caucasian/White	405 participants n=5 Participants	411 participants n=7 Participants	816 participants n=5 Participants
Race/Ethnicity, Customized Black	10 participants n=5 Participants	7 participants n=7 Participants	17 participants n=5 Participants
Race/Ethnicity, Customized Asian/Oriental	40 participants n=5 Participants	34 participants n=7 Participants	74 participants n=5 Participants
Race/Ethnicity, Customized Other	2 participants n=5 Participants	4 participants n=7 Participants	6 participants n=5 Participants
Body Surface Area (BSA)	1.8 m² STANDARD_DEVIATION 0.2 • n=5 Participants	1.8 m² STANDARD_DEVIATION 0.2 • n=7 Participants	1.8 m² STANDARD_DEVIATION 0.2 • n=5 Participants
Prior Bevacizumab (as per IVRS) Yes	53 participants n=5 Participants	51 participants n=7 Participants	104 participants n=5 Participants
Prior Bevacizumab (as per IVRS) No	404 participants n=5 Participants	405 participants n=7 Participants	809 participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) performance status score (as per IVRS) Participants with ECOG Score = 0	151 participants n=5 Participants	149 participants n=7 Participants	300 participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) performance status score (as per IVRS) Participants with ECOG Score = 1	283 participants n=5 Participants	286 participants n=7 Participants	569 participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) performance status score (as per IVRS) Participants with ECOG Score = 2	23 participants n=5 Participants	21 participants n=7 Participants	44 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline to the date when 687 deaths occurred (26 January 2011)

Population: All randomized participants.

Outcome measures

Outcome measures
Measure	Placebo/Docetaxel n=344 Events (Death) Participants with Non-Small-Cell Lung Cancer (NSCLC) were administered Placebo immediately followed by Docetaxel every three weeks until disease progression, unacceptable toxicity, or participant's refusal.	Aflibercept/Docetaxel n=343 Events (Death) Participants with Non-Small-Cell Lung Cancer (NSCLC) were administered Aflibercept immediately followed by Docetaxel every three weeks until disease progression, unacceptable toxicity, or participant's refusal.
Overall Survival (OS)	10.41 months Interval 9.199 to 11.86	10.05 months Interval 9.166 to 11.598

SECONDARY outcome

Timeframe: Baseline to data cut-off (26 January 2011)

Population: Intent to treat (ITT) population. The results are based on a total of 865 PFS events (434 in the placebo group and 431 in the aflibercept group) at the time of cutoff.

PFS was defined as the time interval between the date of randomization and the time of occurrence of the first radiological tumor progression detected by a computer tomography (CT) scan and /or by Magnetic Resonance Imaging (MRI); or death due to any cause; whichever was earlier. Participants without disease progression were censored at the earliest date between their last valid tumour assessment and the data cutoff date. PFS was estimated from Kaplan-Meier Curves.

Outcome measures

Outcome measures
Measure	Placebo/Docetaxel n=434 PFS Events Participants with Non-Small-Cell Lung Cancer (NSCLC) were administered Placebo immediately followed by Docetaxel every three weeks until disease progression, unacceptable toxicity, or participant's refusal.	Aflibercept/Docetaxel n=431 PFS Events Participants with Non-Small-Cell Lung Cancer (NSCLC) were administered Aflibercept immediately followed by Docetaxel every three weeks until disease progression, unacceptable toxicity, or participant's refusal.
Progression Free Survival (PFS)	4.11 months Interval 3.515 to 4.337	5.19 months Interval 4.37 to 5.552

SECONDARY outcome

Timeframe: Baseline to data cut-off (26 January 2011)

Population: Evaluable population: All ITT participants with measurable disease at study entry, and with at least one valid post baseline tumor evaluation, except if the participant died due to progressive disease or had documented (ie, radiological) progression before having any post-baseline tumor evaluation.

Participants with OR were those who had a confirmed complete response \[CR\] or a confirmed partial response \[PR\], based on RECIST criteria, in which * CR refected the disappearance of all tumor lesions (with no new tumors) * PR reflected a pre-defined decrease in tumor burden - a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD * OR was CR + PR The response rate was the percent of participants with a response. To determine a response, tumors were assessed by the investigators using Computerized Tomography (CT) scans or Magnetic Resonance Imaging (MRI) scans; and an observed response was confirmed by repeated imaging after 4 - 6 weeks.

Outcome measures

Outcome measures
Measure	Placebo/Docetaxel n=406 Participants Participants with Non-Small-Cell Lung Cancer (NSCLC) were administered Placebo immediately followed by Docetaxel every three weeks until disease progression, unacceptable toxicity, or participant's refusal.	Aflibercept/Docetaxel n=404 Participants Participants with Non-Small-Cell Lung Cancer (NSCLC) were administered Aflibercept immediately followed by Docetaxel every three weeks until disease progression, unacceptable toxicity, or participant's refusal.
Overall Response (OR) Rate as Per Response Evaluation Criteria in Solid Tumours (RECIST) Criteria Overall Response (OR) rate	8.9 percentage of participants	38.6 percentage of participants
Overall Response (OR) Rate as Per Response Evaluation Criteria in Solid Tumours (RECIST) Criteria Complete Response (CR) rate	0.2 percentage of participants	0.2 percentage of participants
Overall Response (OR) Rate as Per Response Evaluation Criteria in Solid Tumours (RECIST) Criteria Partial Response (PR) rate	8.6 percentage of participants	23.0 percentage of participants

SECONDARY outcome

Timeframe: Baseline (prior to first dose), at cycles 2 and 4 and at the end of study therapy.

Population: ITT population with questionnaires evaluable for LCSS.

HRQL assessments were performed by participants using a self-administered LCSS questionnaire. LCSS is a 9-item questionnaire, six measuring major symptoms for lung malignancies (appetite, fatigue, cough, dyspnea, hemoptysis and pain), and 3 summation items related to total symptomatic distress, activity status and overall quality of life. Participant responses were measured using visual analogue scales (VAS) with 100-mm lines. The LCSS total score was defined as the mean of the 9 items of the scale, each scored between 0 (for best outcome) to 100 (for worst outcome).

Outcome measures

Outcome measures
Measure	Placebo/Docetaxel n=457 Participants Participants with Non-Small-Cell Lung Cancer (NSCLC) were administered Placebo immediately followed by Docetaxel every three weeks until disease progression, unacceptable toxicity, or participant's refusal.	Aflibercept/Docetaxel n=456 Participants Participants with Non-Small-Cell Lung Cancer (NSCLC) were administered Aflibercept immediately followed by Docetaxel every three weeks until disease progression, unacceptable toxicity, or participant's refusal.
Health Related Quality of Life (HRQL) Assessed by the Lung Cancer Symptom Scale (LCSS) Baseline (N=431, N=428)	29.52 units on a scale Standard Deviation 17.03	31.54 units on a scale Standard Deviation 18.03
Health Related Quality of Life (HRQL) Assessed by the Lung Cancer Symptom Scale (LCSS) Cycle 2 (N=329, N=315)	29.50 units on a scale Standard Deviation 16.72	30.54 units on a scale Standard Deviation 16.78
Health Related Quality of Life (HRQL) Assessed by the Lung Cancer Symptom Scale (LCSS) Cycle 4 (N=211, N=240)	27.67 units on a scale Standard Deviation 16.24	29.61 units on a scale Standard Deviation 16.92
Health Related Quality of Life (HRQL) Assessed by the Lung Cancer Symptom Scale (LCSS) End of treatment (N=254, N=240)	34.82 units on a scale Standard Deviation 18.34	36.07 units on a scale Standard Deviation 18.81

SECONDARY outcome

Timeframe: Baseline (prior to first dose), at cycles 2 and 4 and at the end of study therapy.

Population: ITT population with questionnaires evaluable for ABSI.

HRQL assessments were performed by participants using a self-administered LCSS questionnaire. LCSS is a 9-item questionnaire, six measuring major symptoms for lung malignancies, and 3 summation items related to total symptomatic distress, activity status and overall quality of life. Participant responses were measured using visual analogue scales (VAS) with 100-mm lines. ABSI was the mean score for the six major lung cancer symptoms (appetite, fatigue, cough, dyspnea, hemoptysis and pain), each scored between 0 (for best outcome) to 100 (for worst outcome).

Outcome measures

Outcome measures
Measure	Placebo/Docetaxel n=457 Participants Participants with Non-Small-Cell Lung Cancer (NSCLC) were administered Placebo immediately followed by Docetaxel every three weeks until disease progression, unacceptable toxicity, or participant's refusal.	Aflibercept/Docetaxel n=456 Participants Participants with Non-Small-Cell Lung Cancer (NSCLC) were administered Aflibercept immediately followed by Docetaxel every three weeks until disease progression, unacceptable toxicity, or participant's refusal.
Health Related Quality of Life (HRQL) Assessed by the Average Symptom Burden Index (ASBI) Cycle 4 (N=211, N=241)	24.52 units on a scale Standard Deviation 15.22	26.19 units on a scale Standard Deviation 16.38
Health Related Quality of Life (HRQL) Assessed by the Average Symptom Burden Index (ASBI) End of treatment (N=253, N=239)	30.73 units on a scale Standard Deviation 17.26	31.19 units on a scale Standard Deviation 18.12
Health Related Quality of Life (HRQL) Assessed by the Average Symptom Burden Index (ASBI) Baseline (N=429, N=429)	26.17 units on a scale Standard Deviation 16.30	28.24 units on a scale Standard Deviation 16.91
Health Related Quality of Life (HRQL) Assessed by the Average Symptom Burden Index (ASBI) Cycle 2 (N=327, N=316)	26.23 units on a scale Standard Deviation 15.93	27.05 units on a scale Standard Deviation 15.92

Adverse Events

Placebo/Docetaxel

Serious events: 159 serious events

Other events: 388 other events

Deaths: 0 deaths

Aflibercept/Docetaxel

Serious events: 218 serious events

Other events: 402 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Trial Transparency Team

Sanofi-aventis

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The investigator shall have the right to independently publish study results from his site after a multicenter publication, or 12 months after the completion of the study by all sites. He must provide the sponsor a copy of any such publication derived from the study for review and comment at least 30 days in advance of any submission, and delay publication till the approval of the publication is given in writing by the Sponsor (not to exceed 90 days).
Publication restrictions are in place

Restriction type: OTHER

Serious adverse events
Measure	Placebo/Docetaxel n=453 participants at risk Participants with Non-Small-Cell Lung Cancer (NSCLC) were administered Placebo immediately followed by Docetaxel every three weeks until disease progression, unacceptable toxicity, or participant's refusal.	Aflibercept/Docetaxel n=452 participants at risk Participants with Non-Small-Cell Lung Cancer (NSCLC) were administered Aflibercept immediately followed by Docetaxel every three weeks until disease progression, unacceptable toxicity, or participant's refusal.
Skin and subcutaneous tissue disorders Hyperkeratosis	0.00% 0/453 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.	0.22% 1/452 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.
Musculoskeletal and connective tissue disorders Bone pain	0.00% 0/453 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.	0.44% 2/452 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/453 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.	0.22% 1/452 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.00% 0/453 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.	0.22% 1/452 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.
Musculoskeletal and connective tissue disorders Muscle spasms	0.22% 1/453 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.	0.00% 0/452 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.
Musculoskeletal and connective tissue disorders Neck pain	0.00% 0/453 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.	0.22% 1/452 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.
Musculoskeletal and connective tissue disorders Hypercreatinaemia	0.22% 1/453 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.	0.00% 0/452 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.
Musculoskeletal and connective tissue disorders Myositis	0.22% 1/453 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.	0.00% 0/452 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.
Infections and infestations Pneumonia	4.4% 20/453 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.	3.3% 15/452 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.
Infections and infestations Urinary tract infection	0.22% 1/453 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.	0.00% 0/452 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.
Infections and infestations Bronchitis	0.22% 1/453 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.	0.88% 4/452 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.
Infections and infestations Neutropenic infection	2.4% 11/453 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.	2.4% 11/452 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.
Infections and infestations Respiratory tract infection	1.5% 7/453 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.	0.88% 4/452 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.
Infections and infestations Upper respiratory tract infection	0.00% 0/453 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.	0.22% 1/452 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.
Infections and infestations Lower respiratory tract infection	0.66% 3/453 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.	0.44% 2/452 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.
Infections and infestations Neutropenic sepsis	0.66% 3/453 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.	2.2% 10/452 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.
Infections and infestations Lung infection	0.22% 1/453 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.	0.22% 1/452 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.
Infections and infestations Cellulitis	0.00% 0/453 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.	0.22% 1/452 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.
Infections and infestations Anal abscess	0.00% 0/453 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.	0.22% 1/452 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.
Infections and infestations Gastroenteritis	0.00% 0/453 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.	0.22% 1/452 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.
Infections and infestations Pneumonia necrotising	0.00% 0/453 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.	0.44% 2/452 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.
Infections and infestations Sepsis	0.22% 1/453 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.	0.44% 2/452 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.
Infections and infestations Empyema	0.22% 1/453 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.	0.22% 1/452 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.
Infections and infestations Groin abscess	0.00% 0/453 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.	0.22% 1/452 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.
Infections and infestations Hepatitis c	0.44% 2/453 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.	0.00% 0/452 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.
Infections and infestations Lobar pneumonia	0.22% 1/453 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.	0.22% 1/452 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.
Infections and infestations Lung abscess	0.00% 0/453 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.	0.44% 2/452 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.
Infections and infestations Skin infection	0.00% 0/453 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.	0.22% 1/452 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.
Infections and infestations Abscess limb	0.00% 0/453 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.	0.22% 1/452 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.
Infections and infestations Diverticulitis	0.00% 0/453 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.	0.22% 1/452 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.
Infections and infestations Gastroenteritis viral	0.00% 0/453 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.	0.22% 1/452 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.
Infections and infestations Infected skin ulcer	0.00% 0/453 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.	0.22% 1/452 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.
Infections and infestations Lower respiratory tract infection bacterial	0.22% 1/453 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.	0.00% 0/452 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.
Infections and infestations Perineal abscess	0.00% 0/453 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.	0.22% 1/452 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.
Infections and infestations Pneumonia moraxella	0.22% 1/453 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.	0.00% 0/452 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.
Infections and infestations Pneumonia staphylococcal	0.00% 0/453 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.	0.22% 1/452 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.
Infections and infestations Pulmonary tuberculosis	0.22% 1/453 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.	0.00% 0/452 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.
Infections and infestations Septic shock	0.22% 1/453 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.	0.00% 0/452 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour pain	0.00% 0/453 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.	0.22% 1/452 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cancer pain	0.00% 0/453 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.	0.22% 1/452 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.

Other adverse events
Measure	Placebo/Docetaxel n=453 participants at risk Participants with Non-Small-Cell Lung Cancer (NSCLC) were administered Placebo immediately followed by Docetaxel every three weeks until disease progression, unacceptable toxicity, or participant's refusal.	Aflibercept/Docetaxel n=452 participants at risk Participants with Non-Small-Cell Lung Cancer (NSCLC) were administered Aflibercept immediately followed by Docetaxel every three weeks until disease progression, unacceptable toxicity, or participant's refusal.
Vascular disorders Hypertension	5.1% 23/453 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.	21.0% 95/452 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.
Respiratory, thoracic and mediastinal disorders Cough	20.8% 94/453 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.	23.9% 108/452 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.
Respiratory, thoracic and mediastinal disorders Dyspnoea	19.6% 89/453 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.	18.8% 85/452 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.
Metabolism and nutrition disorders Decreased appetite	20.5% 93/453 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.	27.0% 122/452 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.
Nervous system disorders Peripheral sensory neuropathy	14.3% 65/453 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.	11.9% 54/452 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.
Nervous system disorders Headache	6.0% 27/453 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.	13.1% 59/452 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.
Nervous system disorders Dysgeusia	3.3% 15/453 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.	7.7% 35/452 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.
Nervous system disorders Paraesthesia	6.0% 27/453 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.	4.4% 20/452 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.
Eye disorders Lacrimation increased	4.0% 18/453 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.	9.1% 41/452 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.
Respiratory, thoracic and mediastinal disorders Epistaxis	6.2% 28/453 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.	19.9% 90/452 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.
Respiratory, thoracic and mediastinal disorders Dysphonia	3.5% 16/453 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.	18.4% 83/452 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.
Respiratory, thoracic and mediastinal disorders Haemoptysis	5.1% 23/453 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.	5.3% 24/452 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.
Gastrointestinal disorders Stomatitis	15.2% 69/453 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.	39.8% 180/452 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.
Gastrointestinal disorders Diarrhoea	23.4% 106/453 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.	27.4% 124/452 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.
Gastrointestinal disorders Nausea	20.3% 92/453 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.	17.5% 79/452 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.
Gastrointestinal disorders Constipation	12.1% 55/453 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.	14.4% 65/452 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.
Gastrointestinal disorders Vomiting	12.4% 56/453 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.	12.6% 57/452 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.
Gastrointestinal disorders Abdominal pain	5.5% 25/453 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.	4.4% 20/452 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.
Gastrointestinal disorders Dysphagia	1.3% 6/453 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.	5.1% 23/452 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.
Skin and subcutaneous tissue disorders Alopecia	32.7% 148/453 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.	29.4% 133/452 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.
Skin and subcutaneous tissue disorders Nail disorder	7.3% 33/453 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.	9.3% 42/452 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.
Skin and subcutaneous tissue disorders Rash	5.7% 26/453 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.	6.6% 30/452 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysaesthesia syndrome	1.3% 6/453 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.	6.2% 28/452 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.
Musculoskeletal and connective tissue disorders Back pain	6.4% 29/453 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.	9.5% 43/452 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.
Musculoskeletal and connective tissue disorders Myalgia	6.8% 31/453 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.	8.4% 38/452 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.
Musculoskeletal and connective tissue disorders Arthralgia	7.9% 36/453 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.	6.9% 31/452 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.
Musculoskeletal and connective tissue disorders Bone pain	4.9% 22/453 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.	6.0% 27/452 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.
Musculoskeletal and connective tissue disorders Pain in extremity	5.5% 25/453 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.	4.4% 20/452 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	5.3% 24/453 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.	4.2% 19/452 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.
Renal and urinary disorders Proteinuria	0.88% 4/453 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.	7.5% 34/452 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.
General disorders Fatigue	28.7% 130/453 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.	31.4% 142/452 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.
General disorders Asthenia	18.5% 84/453 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.	18.4% 83/452 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.
General disorders Pyrexia	9.3% 42/453 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.	11.7% 53/452 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.
General disorders Oedema peripheral	11.9% 54/453 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.	6.4% 29/452 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.
General disorders Non-cardiac chest pain	6.4% 29/453 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.	7.1% 32/452 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.
Investigations Weight decreased	7.7% 35/453 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.	24.3% 110/452 • From treatment initiation to October 21, 2011 A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.