Trial Outcomes & Findings for Chemotherapy With or Without Bevacizumab in Treating Patients With Stage IB, Stage II, or Stage IIIA Non-small Cell Lung Cancer That Was Removed By Surgery (NCT NCT00324805)

NCT ID: NCT00324805

Last Updated: 2025-03-03

Results Overview

Overall survival (OS) was defined as the time from randomization to death from any cause, and patients who were thought to be alive at the time of final analysis were censored at the last date of contact. The study failed to meet its primary endpoint.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 1501 participants
• Primary outcome timeframe: From registration to death, up to 10 years
• Results posted on: 2025-03-03

Participant Flow

Patients were recruited between June 1, 2007 and September 20, 2013 from ECOG-ACRIN, SWOG, RTOG, CALGB, NCCTG, NCIC-CTG, NSABP, ACOSOG, and CTSU sites.

Participant milestones

Measure	Arm I (Chemotherapy) Patients receive one of the following. For all, treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. REGIMEN 1: Vinorelbine ditartrate 30 mg/m2 intravenously (IV) on days 1 and 8, cisplatin 75 mg/m2 IV over 60 minutes on day 1 REGIMEN 2: Docetaxel 75 mg/m2 IV and cisplastin 75 mg/m2 IV on day 1 REGIMEN 3: Gemcitabine hydrochloride 1200 mg/m2 IV on days 1 and 8, cisplatin 75 mg/m2 IV on day 1 REGIMEN 4 (non-squamous histology only): Pemetrexed disodium 500mg/m2 IV and cisplatin 75 mg/m2 IV on day 1 Cisplatin: Given IV Docetaxel: Given IV Gemcitabine Hydrochloride: Given IV Pemetrexed Disodium: Given IV Vinorelbine: Given IV	Arm II (Chemotherapy, Bevacizumab) Patients receive chemotherapy as in Arm I. Patients also receive bevacizumab IV over 30-90 minutes on day 1. Treatment with bevacizumab repeats every 21 days for up to 1 year. Bevacizumab: Given IV Cisplatin: Given IV Docetaxel: Given IV Gemcitabine Hydrochloride: Given IV Pemetrexed Disodium: Given IV Vinorelbine: Given IV
Overall Study STARTED	749	752
Overall Study Started Assigned Therapy	737	735
Overall Study COMPLETED	599	269
Overall Study NOT COMPLETED	150	483

Reasons for withdrawal

Measure	Arm I (Chemotherapy) Patients receive one of the following. For all, treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. REGIMEN 1: Vinorelbine ditartrate 30 mg/m2 intravenously (IV) on days 1 and 8, cisplatin 75 mg/m2 IV over 60 minutes on day 1 REGIMEN 2: Docetaxel 75 mg/m2 IV and cisplastin 75 mg/m2 IV on day 1 REGIMEN 3: Gemcitabine hydrochloride 1200 mg/m2 IV on days 1 and 8, cisplatin 75 mg/m2 IV on day 1 REGIMEN 4 (non-squamous histology only): Pemetrexed disodium 500mg/m2 IV and cisplatin 75 mg/m2 IV on day 1 Cisplatin: Given IV Docetaxel: Given IV Gemcitabine Hydrochloride: Given IV Pemetrexed Disodium: Given IV Vinorelbine: Given IV	Arm II (Chemotherapy, Bevacizumab) Patients receive chemotherapy as in Arm I. Patients also receive bevacizumab IV over 30-90 minutes on day 1. Treatment with bevacizumab repeats every 21 days for up to 1 year. Bevacizumab: Given IV Cisplatin: Given IV Docetaxel: Given IV Gemcitabine Hydrochloride: Given IV Pemetrexed Disodium: Given IV Vinorelbine: Given IV
Overall Study Adverse Event	62	203
Overall Study Progression	7	35
Overall Study Withdrawal by Subject	51	174
Overall Study Death	6	9
Overall Study Alternative therapy	4	8
Overall Study Other complicating disease	1	9
Overall Study Other reasons	7	26
Overall Study Other	0	2
Overall Study Did not start therapy	12	17

Baseline Characteristics

Chemotherapy With or Without Bevacizumab in Treating Patients With Stage IB, Stage II, or Stage IIIA Non-small Cell Lung Cancer That Was Removed By Surgery

Baseline characteristics by cohort

Measure	Arm I (Chemotherapy) n=749 Participants Patients receive one of the following. For all, treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. REGIMEN 1: Vinorelbine ditartrate 30 mg/m2 IV on days 1 and 8, cisplatin 75 mg/m2 IV over 60 minutes on day 1 REGIMEN 2: Docetaxel 75 mg/m2 IV and cisplastin 75 mg/m2 IV on day 1 REGIMEN 3: Gemcitabine hydrochloride 1200 mg/m2 IV on days 1 and 8, cisplatin 75 mg/m2 IV on day 1 REGIMEN 4 (non-squamous histology only): Pemetrexed disodium 500mg/m2 IV and cisplatin 75 mg/m2 IV on day 1 Cisplatin: Given IV Docetaxel: Given IV Gemcitabine Hydrochloride: Given IV Pemetrexed Disodium: Given IV Vinorelbine: Given IV	Arm II (Chemotherapy, Bevacizumab) n=752 Participants Patients receive chemotherapy as in Arm I. Patients also receive bevacizumab IV over 30-90 minutes on day 1. Treatment with bevacizumab repeats every 21 days for up to 1 year. Bevacizumab: Given IV Cisplatin: Given IV Docetaxel: Given IV Gemcitabine Hydrochloride: Given IV Pemetrexed Disodium: Given IV Vinorelbine: Given IV	Total n=1501 Participants Total of all reporting groups
Age, Continuous	60.7 years STANDARD_DEVIATION 9.0 • n=5 Participants	60.8 years STANDARD_DEVIATION 8.7 • n=7 Participants	60.8 years STANDARD_DEVIATION 8.8 • n=5 Participants
Sex: Female, Male Female	374 Participants n=5 Participants	381 Participants n=7 Participants	755 Participants n=5 Participants
Sex: Female, Male Male	375 Participants n=5 Participants	371 Participants n=7 Participants	746 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	19 Participants n=5 Participants	29 Participants n=7 Participants	48 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	680 Participants n=5 Participants	688 Participants n=7 Participants	1368 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	50 Participants n=5 Participants	35 Participants n=7 Participants	85 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	5 Participants n=7 Participants	6 Participants n=5 Participants
Race (NIH/OMB) Asian	22 Participants n=5 Participants	16 Participants n=7 Participants	38 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) Black or African American	74 Participants n=5 Participants	57 Participants n=7 Participants	131 Participants n=5 Participants
Race (NIH/OMB) White	642 Participants n=5 Participants	660 Participants n=7 Participants	1302 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	7 Participants n=5 Participants	12 Participants n=7 Participants	19 Participants n=5 Participants
Chemotherapy Cisplatin/Vinorelbine	187 Participants n=5 Participants	190 Participants n=7 Participants	377 Participants n=5 Participants
Chemotherapy Cisplatin/Docetaxel	172 Participants n=5 Participants	171 Participants n=7 Participants	343 Participants n=5 Participants
Chemotherapy Cisplatin/Gemcitabine	142 Participants n=5 Participants	141 Participants n=7 Participants	283 Participants n=5 Participants
Chemotherapy Cisplatin/Pemetrexed	248 Participants n=5 Participants	249 Participants n=7 Participants	497 Participants n=5 Participants
Chemotherapy Unknown/Missing	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Histology Squamous	216 Participants n=5 Participants	206 Participants n=7 Participants	422 Participants n=5 Participants
Histology Adenocarcinoma	424 Participants n=5 Participants	450 Participants n=7 Participants	874 Participants n=5 Participants
Histology Large cell	22 Participants n=5 Participants	16 Participants n=7 Participants	38 Participants n=5 Participants
Histology Bronchioloalveolar carcinoma (BAC)	8 Participants n=5 Participants	5 Participants n=7 Participants	13 Participants n=5 Participants
Histology Not otherwise specified (NOS)	24 Participants n=5 Participants	16 Participants n=7 Participants	40 Participants n=5 Participants
Histology Combined/mixed	45 Participants n=5 Participants	48 Participants n=7 Participants	93 Participants n=5 Participants
Histology Other	10 Participants n=5 Participants	10 Participants n=7 Participants	20 Participants n=5 Participants
Histology Unknown/missing	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Performance Status Fully active	439 Participants n=5 Participants	440 Participants n=7 Participants	879 Participants n=5 Participants
Performance Status Ambulatory	310 Participants n=5 Participants	310 Participants n=7 Participants	620 Participants n=5 Participants
Performance Status Unknown/missing	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Urine protein:creatinine (UPC) ratio	0.31 ratio STANDARD_DEVIATION 3.10 • n=5 Participants	0.18 ratio STANDARD_DEVIATION 0.92 • n=7 Participants	0.25 ratio STANDARD_DEVIATION 2.28 • n=5 Participants
Urine protein	95.26 mg/dL STANDARD_DEVIATION 32.28 • n=5 Participants	100.25 mg/dL STANDARD_DEVIATION 32.28 • n=7 Participants	97.79 mg/dL STANDARD_DEVIATION 41.86 • n=5 Participants

PRIMARY outcome

Timeframe: From registration to death, up to 10 years

Population: All enrolled patients

Overall survival (OS) was defined as the time from randomization to death from any cause, and patients who were thought to be alive at the time of final analysis were censored at the last date of contact. The study failed to meet its primary endpoint.

Outcome measures

Measure	Arm I (Chemotherapy) n=749 Participants Patients receive one of the following. For all, treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. REGIMEN 1: Vinorelbine ditartrate 30 mg/m2 IV on days 1 and 8, cisplatin 75 mg/m2 IV over 60 minutes on day 1 REGIMEN 2: Docetaxel 75 mg/m2 IV and cisplastin 75 mg/m2 IV on day 1 REGIMEN 3: Gemcitabine hydrochloride 1200 mg/m2 IV on days 1 and 8, cisplatin 75 mg/m2 IV on day 1 REGIMEN 4 (non-squamous histology only): Pemetrexed disodium 500mg/m2 IV and cisplatin 75 mg/m2 IV on day 1 Cisplatin: Given IV Docetaxel: Given IV Gemcitabine Hydrochloride: Given IV Pemetrexed Disodium: Given IV Vinorelbine: Given IV	Arm II (Chemotherapy, Bevacizumab) n=752 Participants Patients receive chemotherapy as in Arm I. Patients also receive bevacizumab IV over 30-90 minutes on day 1. Treatment with bevacizumab repeats every 21 days for up to 1 year. Bevacizumab: Given IV Cisplatin: Given IV Docetaxel: Given IV Gemcitabine Hydrochloride: Given IV Pemetrexed Disodium: Given IV Vinorelbine: Given IV
Overall Survival	NA months The median overall survival and corresponding 95% confidence interval were not calculable because an insufficient number of participants reached the event at the final time point for assessment, i.e. a median has not been reached	85.8 months Interval 74.9 to The upper limit of the 95% confidence interval was not calculable because an insufficient number of participants reached the event at the final time point for assessment.

SECONDARY outcome

Timeframe: From registration to death, up to 10 years

Population: All enrolled patients

Disease-free survival (DFS) was defined as the time from randomization to an event. Events include disease recurrence, new primary of lung cancer, second primaries or death, whichever occurred first; however, it should be noted that patients with new primaries at other non-lung sites should have continued followup for recurrence of the original cancer. Patients that have not had an event reported at analysis were censored at their last date of disease assessment.

Outcome measures

Measure	Arm I (Chemotherapy) n=749 Participants Patients receive one of the following. For all, treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. REGIMEN 1: Vinorelbine ditartrate 30 mg/m2 IV on days 1 and 8, cisplatin 75 mg/m2 IV over 60 minutes on day 1 REGIMEN 2: Docetaxel 75 mg/m2 IV and cisplastin 75 mg/m2 IV on day 1 REGIMEN 3: Gemcitabine hydrochloride 1200 mg/m2 IV on days 1 and 8, cisplatin 75 mg/m2 IV on day 1 REGIMEN 4 (non-squamous histology only): Pemetrexed disodium 500mg/m2 IV and cisplatin 75 mg/m2 IV on day 1 Cisplatin: Given IV Docetaxel: Given IV Gemcitabine Hydrochloride: Given IV Pemetrexed Disodium: Given IV Vinorelbine: Given IV	Arm II (Chemotherapy, Bevacizumab) n=752 Participants Patients receive chemotherapy as in Arm I. Patients also receive bevacizumab IV over 30-90 minutes on day 1. Treatment with bevacizumab repeats every 21 days for up to 1 year. Bevacizumab: Given IV Cisplatin: Given IV Docetaxel: Given IV Gemcitabine Hydrochloride: Given IV Pemetrexed Disodium: Given IV Vinorelbine: Given IV
Disease-free Survival	42.9 months Interval 36.7 to 57.0	40.6 months Interval 35.5 to 49.5

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 1 year post-treatment

If the difference in the rate of a particular category of toxicities between the 2 arms (N=750 per arm) is at least 5% (4% vs. 9%), 96% power can be attained assuming a significance level of 5% (two-sided Chi Square test) and that the lower toxicity rate for one arm is 4%. A difference in the rates of grade 3-5 arterial thromboembolic events and bleeding events will be monitored and assessed between the treatment arms.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: From registration to death, up to 10 years

Population: Data for these studies were not collected

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: From registration to death, up to 10 years

Population: Data were not collected

Outcome measures

Outcome data not reported

Adverse Events

Arm I (Chemotherapy)

Serious events: 424 serious events

Other events: 474 other events

Deaths: 0 deaths

Arm II (Chemotherapy, Bevacizumab)

Serious events: 563 serious events

Other events: 509 other events

Deaths: 0 deaths

Serious adverse events

Measure	Arm I (Chemotherapy) n=738 participants at risk Patients receive one of the following. For all, treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. REGIMEN 1: Vinorelbine ditartrate 30 mg/m2 IV on days 1 and 8, cisplatin 75 mg/m2 IV over 60 minutes on day 1 REGIMEN 2: Docetaxel 75 mg/m2 IV and cisplastin 75 mg/m2 IV on day 1 REGIMEN 3: Gemcitabine hydrochloride 1200 mg/m2 IV on days 1 and 8, cisplatin 75 mg/m2 IV on day 1 REGIMEN 4 (non-squamous histology only): Pemetrexed disodium 500mg/m2 IV and cisplatin 75 mg/m2 IV on day 1 Cisplatin: Given IV Docetaxel: Given IV Gemcitabine Hydrochloride: Given IV Pemetrexed Disodium: Given IV Vinorelbine: Given IV	Arm II (Chemotherapy, Bevacizumab) n=735 participants at risk Patients receive chemotherapy as in Arm I. Patients also receive bevacizumab IV over 30-90 minutes on day 1. Treatment with bevacizumab repeats every 21 days for up to 1 year. Bevacizumab: Given IV Cisplatin: Given IV Docetaxel: Given IV Gemcitabine Hydrochloride: Given IV Pemetrexed Disodium: Given IV Vinorelbine: Given IV
Ear and labyrinth disorders Hearing impaired	0.81% 6/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.27% 2/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Ear and labyrinth disorders Tinnitus	0.54% 4/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.54% 4/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Blood and lymphatic system disorders Anemia	7.0% 52/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	5.4% 40/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Blood and lymphatic system disorders Febrile neutropenia	4.2% 31/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	5.9% 43/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Cardiac disorders Acute coronary syndrome	0.00% 0/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.14% 1/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Cardiac disorders Atrial fibrillation	0.27% 2/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.27% 2/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Cardiac disorders Atrial flutter	0.00% 0/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.14% 1/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Cardiac disorders Cardiac arrest	0.00% 0/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.14% 1/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Cardiac disorders Chest pain - cardiac	0.00% 0/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.14% 1/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Cardiac disorders Heart failure	0.00% 0/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.41% 3/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Cardiac disorders Left ventricular systolic dysfunction	0.14% 1/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.14% 1/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Cardiac disorders Myocardial infarction	0.14% 1/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.95% 7/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Cardiac disorders Sinus tachycardia	0.00% 0/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.27% 2/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Cardiac disorders Cardiac disorders - Other, specify	0.14% 1/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.00% 0/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
General disorders Fatigue	8.9% 66/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	12.5% 92/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
General disorders Fever	0.00% 0/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.27% 2/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
General disorders Infusion site extravasation	0.00% 0/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.14% 1/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
General disorders Multi-organ failure	0.00% 0/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.14% 1/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
General disorders Non-cardiac chest pain	0.41% 3/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.82% 6/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
General disorders Pain	0.27% 2/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.14% 1/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
General disorders Sudden death NOS	0.00% 0/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.14% 1/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Skin and subcutaneous tissue disorders Rash maculo-papular	0.14% 1/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.41% 3/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Skin and subcutaneous tissue disorders Stevens-Johnson syndrome	0.00% 0/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.14% 1/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Gastrointestinal disorders Abdominal distension	0.00% 0/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.27% 2/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Gastrointestinal disorders Abdominal pain	0.68% 5/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	3.0% 22/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Gastrointestinal disorders Cheilitis	0.14% 1/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.00% 0/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Gastrointestinal disorders Colitis	0.68% 5/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.27% 2/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Gastrointestinal disorders Colonic hemorrhage	0.00% 0/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.27% 2/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Gastrointestinal disorders Colonic obstruction	0.00% 0/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.14% 1/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Gastrointestinal disorders Colonic perforation	0.14% 1/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.14% 1/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Gastrointestinal disorders Constipation	1.1% 8/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.68% 5/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Gastrointestinal disorders Diarrhea	2.0% 15/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	4.2% 31/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Gastrointestinal disorders Duodenal perforation	0.00% 0/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.14% 1/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Gastrointestinal disorders Dyspepsia	0.14% 1/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.14% 1/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Gastrointestinal disorders Dysphagia	0.14% 1/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.27% 2/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Gastrointestinal disorders Enterocolitis	0.14% 1/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.14% 1/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Gastrointestinal disorders Esophageal pain	0.14% 1/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.00% 0/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Gastrointestinal disorders Gastric hemorrhage	0.00% 0/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.14% 1/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Gastrointestinal disorders Gastritis	0.14% 1/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.27% 2/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Gastrointestinal disorders Gastroesophageal reflux disease	0.14% 1/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.00% 0/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Gastrointestinal disorders Gastrointestinal pain	0.14% 1/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.00% 0/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Gastrointestinal disorders Ileus	0.41% 3/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.41% 3/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Gastrointestinal disorders Mucositis oral	0.54% 4/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	1.6% 12/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Gastrointestinal disorders Nausea	8.5% 63/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	10.1% 74/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Gastrointestinal disorders Pancreatitis	0.14% 1/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.00% 0/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Gastrointestinal disorders Rectal hemorrhage	0.00% 0/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.27% 2/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Gastrointestinal disorders Small intestinal obstruction	0.14% 1/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.14% 1/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Gastrointestinal disorders Stomach pain	0.14% 1/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.14% 1/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Gastrointestinal disorders Toothache	0.00% 0/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.14% 1/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Gastrointestinal disorders Vomiting	5.1% 38/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	6.4% 47/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Gastrointestinal disorders Gastrointestinal disorders - Other	0.14% 1/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.27% 2/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Hepatobiliary disorders Cholecystitis	0.00% 0/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.14% 1/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Immune system disorders Allergic reaction	0.00% 0/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.14% 1/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Immune system disorders Anaphylaxis	0.95% 7/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.82% 6/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Immune system disorders Autoimmune disorder	0.14% 1/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.00% 0/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Immune system disorders Cytokine release syndrome	0.00% 0/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.14% 1/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Immune system disorders Serum sickness	0.00% 0/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.14% 1/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Infections and infestations Anorectal infection	0.14% 1/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.00% 0/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Infections and infestations Bladder infection	0.00% 0/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.14% 1/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Infections and infestations Bronchial infection	0.41% 3/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.14% 1/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Infections and infestations Catheter related infection	0.00% 0/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.41% 3/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Infections and infestations Device related infection	0.14% 1/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.00% 0/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Infections and infestations Enterocolitis infectious	0.27% 2/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.27% 2/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Infections and infestations Esophageal infection	0.00% 0/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.14% 1/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Infections and infestations Gum infection	0.27% 2/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.00% 0/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Infections and infestations Lung infection	1.1% 8/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	1.5% 11/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Infections and infestations Pleural infection	0.00% 0/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.27% 2/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Infections and infestations Sepsis	0.54% 4/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.68% 5/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Infections and infestations Skin infection	0.27% 2/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.14% 1/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Infections and infestations Tooth infection	0.00% 0/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.14% 1/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Infections and infestations Upper respiratory infection	0.14% 1/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.54% 4/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Infections and infestations Urinary tract infection	0.54% 4/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.68% 5/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Infections and infestations Infections and infestations - Other	1.4% 10/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	2.4% 18/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Injury, poisoning and procedural complications Vascular access complication	0.27% 2/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.41% 3/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Injury, poisoning and procedural complications Wound dehiscence	0.00% 0/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.54% 4/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Investigations Alanine aminotransferase increased	0.27% 2/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.00% 0/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Investigations Alkaline phosphatase increased	0.14% 1/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.00% 0/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Investigations Aspartate aminotransferase increased	0.27% 2/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.00% 0/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Investigations Cardiac troponin I increased	0.14% 1/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.00% 0/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Investigations Creatinine increased	0.81% 6/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	1.2% 9/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Investigations INR increased	0.00% 0/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.14% 1/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Investigations Lipase increased	0.14% 1/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.14% 1/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Investigations Lymphocyte count decreased	0.95% 7/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	1.5% 11/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Investigations Neutrophil count decreased	32.1% 237/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	37.1% 273/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Investigations Platelet count decreased	4.1% 30/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	6.0% 44/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Investigations Weight loss	0.14% 1/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.14% 1/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Investigations White blood cell decreased	5.6% 41/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	5.7% 42/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Investigations Investigations - Other, specify	0.14% 1/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.14% 1/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Metabolism and nutrition disorders Acidosis	0.00% 0/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.27% 2/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Metabolism and nutrition disorders Anorexia	1.2% 9/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	2.6% 19/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Metabolism and nutrition disorders Dehydration	5.4% 40/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	6.1% 45/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Metabolism and nutrition disorders Hypercalcemia	0.14% 1/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.00% 0/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Metabolism and nutrition disorders Hyperglycemia	1.5% 11/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	1.2% 9/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Metabolism and nutrition disorders Hyperkalemia	0.54% 4/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.14% 1/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Metabolism and nutrition disorders Hypoalbuminemia	0.14% 1/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.41% 3/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Metabolism and nutrition disorders Hypocalcemia	0.41% 3/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.82% 6/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Metabolism and nutrition disorders Hypoglycemia	0.00% 0/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.14% 1/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Metabolism and nutrition disorders Hypokalemia	2.7% 20/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	1.8% 13/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Metabolism and nutrition disorders Hypomagnesemia	0.68% 5/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.54% 4/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Metabolism and nutrition disorders Hyponatremia	6.0% 44/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	9.0% 66/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Metabolism and nutrition disorders Hypophosphatemia	0.00% 0/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.54% 4/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Musculoskeletal and connective tissue disorders Arthralgia	0.41% 3/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.68% 5/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.14% 1/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Musculoskeletal and connective tissue disorders Bone pain	0.00% 0/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.14% 1/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Musculoskeletal and connective tissue disorders Chest wall pain	0.00% 0/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.14% 1/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Musculoskeletal and connective tissue disorders Generalized muscle weakness	0.81% 6/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.95% 7/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Musculoskeletal and connective tissue disorders Muscle weakness lower limb	0.00% 0/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.14% 1/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Musculoskeletal and connective tissue disorders Myalgia	0.54% 4/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.27% 2/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Musculoskeletal and connective tissue disorders Neck pain	0.00% 0/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.14% 1/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Musculoskeletal and connective tissue disorders Pain in extremity	0.14% 1/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.14% 1/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Nervous system disorders Ataxia	0.14% 1/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.41% 3/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Nervous system disorders Cognitive disturbance	0.14% 1/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.14% 1/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Nervous system disorders Dizziness	0.54% 4/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	1.6% 12/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Nervous system disorders Dysphasia	0.14% 1/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.14% 1/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Nervous system disorders Headache	0.68% 5/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	2.4% 18/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Nervous system disorders Intracranial hemorrhage	0.14% 1/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.14% 1/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Nervous system disorders Ischemia cerebrovascular	0.00% 0/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.14% 1/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Nervous system disorders Memory impairment	0.00% 0/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.14% 1/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Nervous system disorders Neuralgia	0.00% 0/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.14% 1/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Nervous system disorders Peripheral motor neuropathy	0.27% 2/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.14% 1/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Nervous system disorders Peripheral sensory neuropathy	0.68% 5/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.68% 5/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Nervous system disorders Reversible posterior leukoencephalopathy	0.00% 0/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.41% 3/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Nervous system disorders Seizure	0.14% 1/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.41% 3/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Nervous system disorders Stroke	0.14% 1/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.00% 0/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Nervous system disorders Syncope	1.1% 8/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	1.4% 10/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Nervous system disorders Nervous system disorders - Other	0.00% 0/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.68% 5/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Eye disorders Blurred vision	0.14% 1/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.14% 1/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Eye disorders Photophobia	0.00% 0/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.14% 1/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Eye disorders Retinal detachment	0.00% 0/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.14% 1/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Psychiatric disorders Anxiety	0.14% 1/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.00% 0/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Psychiatric disorders Confusion	0.14% 1/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.54% 4/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Psychiatric disorders Depression	0.41% 3/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.00% 0/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Psychiatric disorders Insomnia	0.00% 0/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.27% 2/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Respiratory, thoracic and mediastinal disorders Aspiration	0.27% 2/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.14% 1/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Respiratory, thoracic and mediastinal disorders Bronchopleural fistula	0.00% 0/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.27% 2/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Respiratory, thoracic and mediastinal disorders Bronchopulmonary hemorrhage	0.00% 0/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.41% 3/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Respiratory, thoracic and mediastinal disorders Cough	0.27% 2/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.82% 6/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Respiratory, thoracic and mediastinal disorders Dyspnea	1.1% 8/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	2.3% 17/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Respiratory, thoracic and mediastinal disorders Epistaxis	0.27% 2/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.54% 4/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Respiratory, thoracic and mediastinal disorders Hoarseness	0.00% 0/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.14% 1/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.68% 5/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Respiratory, thoracic and mediastinal disorders Laryngeal edema	0.00% 0/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.14% 1/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.14% 1/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.27% 2/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.41% 3/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.14% 1/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Respiratory, thoracic and mediastinal disorders Pulmonary hypertension	0.14% 1/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.14% 1/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.14% 1/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Respiratory, thoracic and mediastinal disorders Respiratory thoracic mediastinal - Other	0.14% 1/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.14% 1/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Renal and urinary disorders Acute kidney injury	0.81% 6/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.82% 6/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Renal and urinary disorders Chronic kidney disease	0.14% 1/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.41% 3/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Renal and urinary disorders Hematuria	0.00% 0/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.14% 1/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Renal and urinary disorders Proteinuria	0.27% 2/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	2.3% 17/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Renal and urinary disorders Urinary retention	0.14% 1/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.00% 0/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Reproductive system and breast disorders Testicular pain	0.14% 1/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.00% 0/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Vascular disorders Hematoma	0.00% 0/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.14% 1/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Vascular disorders Hypertension	2.6% 19/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	27.2% 200/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Vascular disorders Hypotension	0.95% 7/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	1.5% 11/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Vascular disorders Peripheral ischemia	0.00% 0/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	0.14% 1/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Vascular disorders Thromboembolic event	1.6% 12/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	4.5% 33/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report

Other adverse events

Measure	Arm I (Chemotherapy) n=738 participants at risk Patients receive one of the following. For all, treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. REGIMEN 1: Vinorelbine ditartrate 30 mg/m2 IV on days 1 and 8, cisplatin 75 mg/m2 IV over 60 minutes on day 1 REGIMEN 2: Docetaxel 75 mg/m2 IV and cisplastin 75 mg/m2 IV on day 1 REGIMEN 3: Gemcitabine hydrochloride 1200 mg/m2 IV on days 1 and 8, cisplatin 75 mg/m2 IV on day 1 REGIMEN 4 (non-squamous histology only): Pemetrexed disodium 500mg/m2 IV and cisplatin 75 mg/m2 IV on day 1 Cisplatin: Given IV Docetaxel: Given IV Gemcitabine Hydrochloride: Given IV Pemetrexed Disodium: Given IV Vinorelbine: Given IV	Arm II (Chemotherapy, Bevacizumab) n=735 participants at risk Patients receive chemotherapy as in Arm I. Patients also receive bevacizumab IV over 30-90 minutes on day 1. Treatment with bevacizumab repeats every 21 days for up to 1 year. Bevacizumab: Given IV Cisplatin: Given IV Docetaxel: Given IV Gemcitabine Hydrochloride: Given IV Pemetrexed Disodium: Given IV Vinorelbine: Given IV
Blood and lymphatic system disorders Anemia	34.7% 256/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	24.9% 183/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
General disorders Fatigue	8.4% 62/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	9.3% 68/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Investigations Creatinine increased	22.9% 169/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	33.6% 247/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Investigations Neutrophil count decreased	29.8% 220/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	32.1% 236/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Investigations Platelet count decreased	6.5% 48/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	6.7% 49/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Nervous system disorders Peripheral sensory neuropathy	7.2% 53/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	7.9% 58/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Renal and urinary disorders Proteinuria	0.41% 3/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	6.5% 48/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report
Vascular disorders Hypertension	0.27% 2/738 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report	6.8% 50/735 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment One patient who did not start treatment submitted an adverse event report

Additional Information

Study Statistician

ECOG-ACRIN Statistical Center

Phone: 617-632-3012

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: LTE60