Trial Outcomes & Findings for A Study of Avastin (Bevacizumab) in Combination With Carboplatin-Based Chemotherapy in Patients With Advanced or Recurrent Non-Squamous Non-Small Cell Lung Cancer. (NCT NCT00700180)

NCT ID: NCT00700180

Last Updated: 2014-09-25

Results Overview

Overall response was analyzed and correlated within dichotomized (low- and high-level) baseline plasma biomarker (basic fibroblast growth factor \[bFGF\], E-selection, intracellular adhesion molecule \[ICAM\], placental growth factor \[PlGF\], vascular endothelial growth factor A \[VEGF A\], vascular endothelial growth factor receptor \[VEGFR\]-1, and VEGFR-2) subgroups: low-level equals (=) less than or equal to (≤) median baseline level, high-level=greater than (\>) median baseline level. Per Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.0 CR defined as disappearance of all target lesions, non-target lesions, and normalization of tumor marker level. PR defined as greater than or equal to (≥)30 percent (%) decrease under baseline of the sum of the longest diameter (LD) of all target lesions. No unequivocal progression of non-target disease; no new lesions. Complete and partial responses must have been confirmed no less than 4 weeks after criteria for response were first met

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 303 participants
• Primary outcome timeframe: Baseline, Day 21 of Cycles 2, 4, and 6 (Bv + chemo), Day 21 of Cycles 7, 8, 9, and 10 (Bv), Day 21 of every other cycle (Bv), and at disease progression.
• Results posted on: 2014-09-25

Participant Flow

Participant milestones

Measure	Bevacizumab 7.5 Milligrams (mg) Plus Chemotherapy Cycles 1-6 (3-week cycles): Participants received bevacizumab 7.5 mg per kilogram (mg/kg) intravenously (IV) on Day 1; either carboplatin at a dose required to achieve an area under the concentration-time curve (AUC) of 6 mg per milliliter (mg/mL) IV and paclitaxel 200 mg per square meter (mg/m\^2) IV on Day 1, or carboplatin at AUC 5 mg/mL IV on Day 1 and gemcitabine 1200 mg/m\^2 IV on Days 1 and 8. The choice of chemotherapy doublet, either carboplatin/paclitaxel or carboplatin/gemcitabine, was left to the discretion of the investigator. The cycle was repeated until disease progression or for a maximum of 6 cycles. Cycle 7 and beyond (3-week cycles): If the first 6 cycles were tolerated with no disease progression, participants then received bevacizumab 7.5 mg/kg IV on Day 1. This cycle was repeated every 3 weeks until disease progression.	Bevacizumab 15 mg Plus Chemotherapy Cycles 1-6 (3-week cycles): Participants received bevacizumab 15 mg/kg IV on Day 1; either carboplatin at a dose required to achieve an AUC of 6 mg/mL IV and paclitaxel 200 mg/m\^2 IV on Day 1, or carboplatin at AUC 5 mg/mL IV on Day 1 and gemcitabine 1200 mg/m\^2 IV on Days 1 and 8. The choice of chemotherapy doublet, either carboplatin/paclitaxel or carboplatin/gemcitabine, was left to the discretion of the investigator. The cycle was repeated until disease progression or for a maximum of 6 cycles. Cycle 7 and beyond (3-week cycles): If the first 6 cycles were tolerated with no disease progression, participants then received bevacizumab 15 mg/kg IV on Day 1. This cycle was repeated every 3 weeks until disease progression.
Overall Study STARTED	154	149
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	154	149

Reasons for withdrawal

Measure	Bevacizumab 7.5 Milligrams (mg) Plus Chemotherapy Cycles 1-6 (3-week cycles): Participants received bevacizumab 7.5 mg per kilogram (mg/kg) intravenously (IV) on Day 1; either carboplatin at a dose required to achieve an area under the concentration-time curve (AUC) of 6 mg per milliliter (mg/mL) IV and paclitaxel 200 mg per square meter (mg/m\^2) IV on Day 1, or carboplatin at AUC 5 mg/mL IV on Day 1 and gemcitabine 1200 mg/m\^2 IV on Days 1 and 8. The choice of chemotherapy doublet, either carboplatin/paclitaxel or carboplatin/gemcitabine, was left to the discretion of the investigator. The cycle was repeated until disease progression or for a maximum of 6 cycles. Cycle 7 and beyond (3-week cycles): If the first 6 cycles were tolerated with no disease progression, participants then received bevacizumab 7.5 mg/kg IV on Day 1. This cycle was repeated every 3 weeks until disease progression.	Bevacizumab 15 mg Plus Chemotherapy Cycles 1-6 (3-week cycles): Participants received bevacizumab 15 mg/kg IV on Day 1; either carboplatin at a dose required to achieve an AUC of 6 mg/mL IV and paclitaxel 200 mg/m\^2 IV on Day 1, or carboplatin at AUC 5 mg/mL IV on Day 1 and gemcitabine 1200 mg/m\^2 IV on Days 1 and 8. The choice of chemotherapy doublet, either carboplatin/paclitaxel or carboplatin/gemcitabine, was left to the discretion of the investigator. The cycle was repeated until disease progression or for a maximum of 6 cycles. Cycle 7 and beyond (3-week cycles): If the first 6 cycles were tolerated with no disease progression, participants then received bevacizumab 15 mg/kg IV on Day 1. This cycle was repeated every 3 weeks until disease progression.
Overall Study Death	99	114
Overall Study Alive on treatment	5	3
Overall Study Alive in follow-up	46	27
Overall Study Lost to Follow-up	4	5

Baseline Characteristics

A Study of Avastin (Bevacizumab) in Combination With Carboplatin-Based Chemotherapy in Patients With Advanced or Recurrent Non-Squamous Non-Small Cell Lung Cancer.

Baseline characteristics by cohort

Measure	Total n=303 Participants Total of all reporting groups	Bevacizumab 7.5 mg Plus Chemotherapy n=154 Participants Cycles 1-6 (3-week cycles): Participants received bevacizumab 7.5 mg/kg IV on Day 1; either carboplatin at a dose required to achieve an AUC of 6 mg/mL IV and paclitaxel 200 mg/m\^2 IV on Day 1, or carboplatin at AUC 5 mg/mL IV on Day 1 and gemcitabine 1200 mg/m\^2 IV on Days 1 and 8. The choice of chemotherapy doublet, either carboplatin/paclitaxel or carboplatin/gemcitabine, was left to the discretion of the investigator. The cycle was repeated until disease progression or for a maximum of 6 cycles. Cycle 7 and beyond (3-week cycles): If the first 6 cycles were tolerated with no disease progression, participants then received bevacizumab 7.5 mg/kg IV on Day 1. This cycle was repeated every 3 weeks until disease progression.	Bevacizumab 15 mg Plus Chemotherapy n=149 Participants Cycles 1-6 (3-week cycles): Participants received bevacizumab 15 mg/kg IV on Day 1; either carboplatin at a dose required to achieve an AUC of 6 mg/mL IV and paclitaxel 200 mg/m\^2 IV on Day 1, or carboplatin at AUC 5 mg/mL IV on Day 1 and gemcitabine 1200 mg/m\^2 IV on Days 1 and 8. The choice of chemotherapy doublet, either carboplatin/paclitaxel or carboplatin/gemcitabine, was left to the discretion of the investigator. The cycle was repeated until disease progression or for a maximum of 6 cycles. Cycle 7 and beyond (3-week cycles): If the first 6 cycles were tolerated with no disease progression, participants then received bevacizumab 15 mg/kg IV on Day 1. This cycle was repeated every 3 weeks until disease progression.
Age, Continuous	59.2 years STANDARD_DEVIATION 10.66 • n=27 Participants	59.7 years STANDARD_DEVIATION 10.13 • n=93 Participants	58.8 years STANDARD_DEVIATION 11.20 • n=4 Participants
Sex: Female, Male Female	111 Participants n=27 Participants	56 Participants n=93 Participants	55 Participants n=4 Participants
Sex: Female, Male Male	192 Participants n=27 Participants	98 Participants n=93 Participants	94 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline, Day 21 of Cycles 2, 4, and 6 (Bv + chemo), Day 21 of Cycles 7, 8, 9, and 10 (Bv), Day 21 of every other cycle (Bv), and at disease progression.

Population: Biomarker Evaluable Protein Plasma (BEP) Population: Participants in the ITT population who started at least 1 dose of bevacizumab and had a non-missing baseline biomarker level determined for at least 1 biomarker. n (number) equals (=) number of participants assessed for the specified biomarker.

Overall response was analyzed and correlated within dichotomized (low- and high-level) baseline plasma biomarker (basic fibroblast growth factor [bFGF], E-selection, intracellular adhesion molecule [ICAM], placental growth factor [PlGF], vascular endothelial growth factor A [VEGF A], vascular endothelial growth factor receptor [VEGFR]-1, and VEGFR-2) subgroups: low-level equals (=) less than or equal to (≤) median baseline level, high-level=greater than (>) median baseline level. Per Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.0 CR defined as disappearance of all target lesions, non-target lesions, and normalization of tumor marker level. PR defined as greater than or equal to (≥)30 percent (%) decrease under baseline of the sum of the longest diameter (LD) of all target lesions. No unequivocal progression of non-target disease; no new lesions. Complete and partial responses must have been confirmed no less than 4 weeks after criteria for response were first met

Outcome measures

Measure	Bevacizumab 7.5 mg Plus Chemotherapy n=82 Participants Cycles 1-6 (3-week cycles): Participants received bevacizumab 7.5 mg/kg IV on Day 1; either carboplatin at a dose required to achieve an AUC of 6 mg/mL IV and paclitaxel 200 mg/m\^2 IV on Day 1, or carboplatin at AUC 5 mg/mL IV on Day 1 and gemcitabine 1200 mg/m\^2 IV on Days 1 and 8. The choice of chemotherapy doublet, either carboplatin/paclitaxel or carboplatin/gemcitabine, was left to the discretion of the investigator. The cycle was repeated until disease progression or for a maximum of 6 cycles. Cycle 7 and beyond (3-week cycles): If the first 6 cycles were tolerated with no disease progression, participants then received bevacizumab 7.5 mg/kg IV on Day 1. This cycle was repeated every 3 weeks until disease progression.	Bevacizumab 15 mg Plus Chemotherapy n=75 Participants Cycles 1-6 (3-week cycles): Participants received bevacizumab 15 mg/kg IV on Day 1; either carboplatin at a dose required to achieve an AUC of 6 mg/mL IV and paclitaxel 200 mg/m\^2 IV on Day 1, or carboplatin at AUC 5 mg/mL IV on Day 1 and gemcitabine 1200 mg/m\^2 IV on Days 1 and 8. The choice of chemotherapy doublet, either carboplatin/paclitaxel or carboplatin/gemcitabine, was left to the discretion of the investigator. The cycle was repeated until disease progression or for a maximum of 6 cycles. Cycle 7 and beyond (3-week cycles): If the first 6 cycles were tolerated with no disease progression, participants then received bevacizumab 15 mg/kg IV on Day 1. This cycle was repeated every 3 weeks until disease progression.
Percentage of Participants With a Best Overall Response of Complete Response (CR) or Partial Response (PR) by Dichotomized Baseline Plasma Marker Level bFGF low level (n=77,65)	42.86 percentage of participants	47.69 percentage of participants
Percentage of Participants With a Best Overall Response of Complete Response (CR) or Partial Response (PR) by Dichotomized Baseline Plasma Marker Level bFGF high level (n=66,75)	34.85 percentage of participants	49.33 percentage of participants
Percentage of Participants With a Best Overall Response of Complete Response (CR) or Partial Response (PR) by Dichotomized Baseline Plasma Marker Level E-selectin low level (n=73,69)	36.99 percentage of participants	42.03 percentage of participants
Percentage of Participants With a Best Overall Response of Complete Response (CR) or Partial Response (PR) by Dichotomized Baseline Plasma Marker Level E-selectin high level (n=70,71)	41.43 percentage of participants	54.93 percentage of participants
Percentage of Participants With a Best Overall Response of Complete Response (CR) or Partial Response (PR) by Dichotomized Baseline Plasma Marker Level ICAM low level (n=70,72)	38.57 percentage of participants	50.00 percentage of participants
Percentage of Participants With a Best Overall Response of Complete Response (CR) or Partial Response (PR) by Dichotomized Baseline Plasma Marker Level ICAM high level (n=29,32	39.73 percentage of participants	47.06 percentage of participants
Percentage of Participants With a Best Overall Response of Complete Response (CR) or Partial Response (PR) by Dichotomized Baseline Plasma Marker Level PlGF low level (n=82, 64)	37.80 percentage of participants	51.56 percentage of participants
Percentage of Participants With a Best Overall Response of Complete Response (CR) or Partial Response (PR) by Dichotomized Baseline Plasma Marker Level PlGF high level (n=27,29)	33.33 percentage of participants	51.72 percentage of participants
Percentage of Participants With a Best Overall Response of Complete Response (CR) or Partial Response (PR) by Dichotomized Baseline Plasma Marker Level VEGF A low level (n=73,67)	42.47 percentage of participants	44.78 percentage of participants
Percentage of Participants With a Best Overall Response of Complete Response (CR) or Partial Response (PR) by Dichotomized Baseline Plasma Marker Level VEGF A high level (n=67,73)	35.82 percentage of participants	53.42 percentage of participants
Percentage of Participants With a Best Overall Response of Complete Response (CR) or Partial Response (PR) by Dichotomized Baseline Plasma Marker Level VEGFR-1 low level (n=72,70)	37.50 percentage of participants	60.00 percentage of participants
Percentage of Participants With a Best Overall Response of Complete Response (CR) or Partial Response (PR) by Dichotomized Baseline Plasma Marker Level VEGFR-1 high level (n=71,70)	40.85 percentage of participants	37.14 percentage of participants
Percentage of Participants With a Best Overall Response of Complete Response (CR) or Partial Response (PR) by Dichotomized Baseline Plasma Marker Level VEGFR-2 low level (n=74,69)	32.43 percentage of participants	46.38 percentage of participants
Percentage of Participants With a Best Overall Response of Complete Response (CR) or Partial Response (PR) by Dichotomized Baseline Plasma Marker Level VEGFR-2 high level (n=69,71)	46.38 percentage of participants	50.70 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Day 1, weekly to disease progression

Population: ITT population.

PFS was defined as the time between randomization and progressive disease (PD) according to RECIST criteria, or death due to any cause. PD was defined as at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started. Disease progression was evaluated according to the RECIST using computed tomography (CT) scans, magnetic resonance imaging (MRI) scans, X-ray, bone scans, or clinical examination. Participants without an event were censored at the date of last follow up for progression. Participants with no post baseline follow-up for progression were censored at the day of randomization.

Outcome measures

Measure	Bevacizumab 7.5 mg Plus Chemotherapy n=154 Participants Cycles 1-6 (3-week cycles): Participants received bevacizumab 7.5 mg/kg IV on Day 1; either carboplatin at a dose required to achieve an AUC of 6 mg/mL IV and paclitaxel 200 mg/m\^2 IV on Day 1, or carboplatin at AUC 5 mg/mL IV on Day 1 and gemcitabine 1200 mg/m\^2 IV on Days 1 and 8. The choice of chemotherapy doublet, either carboplatin/paclitaxel or carboplatin/gemcitabine, was left to the discretion of the investigator. The cycle was repeated until disease progression or for a maximum of 6 cycles. Cycle 7 and beyond (3-week cycles): If the first 6 cycles were tolerated with no disease progression, participants then received bevacizumab 7.5 mg/kg IV on Day 1. This cycle was repeated every 3 weeks until disease progression.	Bevacizumab 15 mg Plus Chemotherapy n=149 Participants Cycles 1-6 (3-week cycles): Participants received bevacizumab 15 mg/kg IV on Day 1; either carboplatin at a dose required to achieve an AUC of 6 mg/mL IV and paclitaxel 200 mg/m\^2 IV on Day 1, or carboplatin at AUC 5 mg/mL IV on Day 1 and gemcitabine 1200 mg/m\^2 IV on Days 1 and 8. The choice of chemotherapy doublet, either carboplatin/paclitaxel or carboplatin/gemcitabine, was left to the discretion of the investigator. The cycle was repeated until disease progression or for a maximum of 6 cycles. Cycle 7 and beyond (3-week cycles): If the first 6 cycles were tolerated with no disease progression, participants then received bevacizumab 15 mg/kg IV on Day 1. This cycle was repeated every 3 weeks until disease progression.
Progression-Free Survival - Percentage of Participants With an Event	83.1 percentage of participants	85.9 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Day 1, weekly to disease progression

Population: ITT Population.

PFS was defined as the time between randomization and disease progression or death due to any cause. Participants without an event were censored at the date of last follow up for progression. Participants with no post baseline follow-up for progression were censored at the day of randomization. Disease progression was evaluated according to the RECIST using CT scans, MRI scans, X-ray, bone scans, or clinical examination. Median PFS was estimated using the Kaplan-Meier method.

Outcome measures

Measure	Bevacizumab 7.5 mg Plus Chemotherapy n=154 Participants Cycles 1-6 (3-week cycles): Participants received bevacizumab 7.5 mg/kg IV on Day 1; either carboplatin at a dose required to achieve an AUC of 6 mg/mL IV and paclitaxel 200 mg/m\^2 IV on Day 1, or carboplatin at AUC 5 mg/mL IV on Day 1 and gemcitabine 1200 mg/m\^2 IV on Days 1 and 8. The choice of chemotherapy doublet, either carboplatin/paclitaxel or carboplatin/gemcitabine, was left to the discretion of the investigator. The cycle was repeated until disease progression or for a maximum of 6 cycles. Cycle 7 and beyond (3-week cycles): If the first 6 cycles were tolerated with no disease progression, participants then received bevacizumab 7.5 mg/kg IV on Day 1. This cycle was repeated every 3 weeks until disease progression.	Bevacizumab 15 mg Plus Chemotherapy n=149 Participants Cycles 1-6 (3-week cycles): Participants received bevacizumab 15 mg/kg IV on Day 1; either carboplatin at a dose required to achieve an AUC of 6 mg/mL IV and paclitaxel 200 mg/m\^2 IV on Day 1, or carboplatin at AUC 5 mg/mL IV on Day 1 and gemcitabine 1200 mg/m\^2 IV on Days 1 and 8. The choice of chemotherapy doublet, either carboplatin/paclitaxel or carboplatin/gemcitabine, was left to the discretion of the investigator. The cycle was repeated until disease progression or for a maximum of 6 cycles. Cycle 7 and beyond (3-week cycles): If the first 6 cycles were tolerated with no disease progression, participants then received bevacizumab 15 mg/kg IV on Day 1. This cycle was repeated every 3 weeks until disease progression.
Progression-Free Survival - Time to Event	6.8 months Interval 5.9 to 7.4	6.7 months Interval 5.9 to 7.2

SECONDARY outcome

Timeframe: Baseline, Day 21 of Cycles 2, 4, and 6, Day 21 of Cycles 7, 8, 9, and 10, Day 21 of every other cycle, and at disease progression

Population: ITT Population. Data for 12 participants (3 at 7.5 mg and 9 at 15 mg) were excluded for reasons including but not limited to: no study treatment (ST), no postbaseline tumor assessment (TA), non-protocol defined antineoplastic therapy before first TA, first TA \>70 days after last dose of last ST, last TA less than (\<) 42 days from start of therapy.

Percentage of participants with CR or PR according to RECIST criteria. Per RECIST v1.0: CR defined as disappearance of all target lesions, non-target lesions, and normalization of tumor marker level. PR was defined as ≥30% decrease under baseline of the sum of the LD of all target lesions. No unequivocal progression of non-target disease. No new lesions. Complete and partial responses were confirmed no less than 4 weeks after the criteria for response were first met.

Outcome measures

Measure	Bevacizumab 7.5 mg Plus Chemotherapy n=154 Participants Cycles 1-6 (3-week cycles): Participants received bevacizumab 7.5 mg/kg IV on Day 1; either carboplatin at a dose required to achieve an AUC of 6 mg/mL IV and paclitaxel 200 mg/m\^2 IV on Day 1, or carboplatin at AUC 5 mg/mL IV on Day 1 and gemcitabine 1200 mg/m\^2 IV on Days 1 and 8. The choice of chemotherapy doublet, either carboplatin/paclitaxel or carboplatin/gemcitabine, was left to the discretion of the investigator. The cycle was repeated until disease progression or for a maximum of 6 cycles. Cycle 7 and beyond (3-week cycles): If the first 6 cycles were tolerated with no disease progression, participants then received bevacizumab 7.5 mg/kg IV on Day 1. This cycle was repeated every 3 weeks until disease progression.	Bevacizumab 15 mg Plus Chemotherapy n=149 Participants Cycles 1-6 (3-week cycles): Participants received bevacizumab 15 mg/kg IV on Day 1; either carboplatin at a dose required to achieve an AUC of 6 mg/mL IV and paclitaxel 200 mg/m\^2 IV on Day 1, or carboplatin at AUC 5 mg/mL IV on Day 1 and gemcitabine 1200 mg/m\^2 IV on Days 1 and 8. The choice of chemotherapy doublet, either carboplatin/paclitaxel or carboplatin/gemcitabine, was left to the discretion of the investigator. The cycle was repeated until disease progression or for a maximum of 6 cycles. Cycle 7 and beyond (3-week cycles): If the first 6 cycles were tolerated with no disease progression, participants then received bevacizumab 15 mg/kg IV on Day 1. This cycle was repeated every 3 weeks until disease progression.
Percentage of Participants With Objective Response	37.1 percentage of participants Interval 29.4 to 45.3	46.4 percentage of participants Interval 38.0 to 55.0

SECONDARY outcome

Timeframe: Baseline, Day 21 of Cycles 2, 4, and 6, Day 21 of Cycles 7, 8, 9, and 10, Day 21 of every other cycle, and at disease progression

Population: ITT Population

Percentage of participants with measurable disease at baseline who on assessment achieved CR, PR, or SD according to RECIST. Per RECIST v1.0: CR defined as disappearance of all target lesions, non-target lesions, and normalization of tumor marker level. PR was defined as ≥30% decrease under baseline of the sum of the LD of all target lesions. No unequivocal progression of non-target disease. No new lesions. SD defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum LD since start of treatment. Complete and partial responses must have been confirmed no less than 4 weeks after the criteria for response were first met. For participants with SD, follow-up assessments must have met the SD criteria at least once after study entry at a minimum interval of 6 weeks.

Outcome measures

Measure	Bevacizumab 7.5 mg Plus Chemotherapy n=151 Participants Cycles 1-6 (3-week cycles): Participants received bevacizumab 7.5 mg/kg IV on Day 1; either carboplatin at a dose required to achieve an AUC of 6 mg/mL IV and paclitaxel 200 mg/m\^2 IV on Day 1, or carboplatin at AUC 5 mg/mL IV on Day 1 and gemcitabine 1200 mg/m\^2 IV on Days 1 and 8. The choice of chemotherapy doublet, either carboplatin/paclitaxel or carboplatin/gemcitabine, was left to the discretion of the investigator. The cycle was repeated until disease progression or for a maximum of 6 cycles. Cycle 7 and beyond (3-week cycles): If the first 6 cycles were tolerated with no disease progression, participants then received bevacizumab 7.5 mg/kg IV on Day 1. This cycle was repeated every 3 weeks until disease progression.	Bevacizumab 15 mg Plus Chemotherapy n=140 Participants Cycles 1-6 (3-week cycles): Participants received bevacizumab 15 mg/kg IV on Day 1; either carboplatin at a dose required to achieve an AUC of 6 mg/mL IV and paclitaxel 200 mg/m\^2 IV on Day 1, or carboplatin at AUC 5 mg/mL IV on Day 1 and gemcitabine 1200 mg/m\^2 IV on Days 1 and 8. The choice of chemotherapy doublet, either carboplatin/paclitaxel or carboplatin/gemcitabine, was left to the discretion of the investigator. The cycle was repeated until disease progression or for a maximum of 6 cycles. Cycle 7 and beyond (3-week cycles): If the first 6 cycles were tolerated with no disease progression, participants then received bevacizumab 15 mg/kg IV on Day 1. This cycle was repeated every 3 weeks until disease progression.
Percentage of Participants With Measurable Disease at Baseline Who Achieved CR, PR, or Stable Disease (SD) for at Least 6 Weeks	76.8 percentage of participants Interval 69.3 to 83.3	78.6 percentage of participants Interval 70.8 to 85.1

SECONDARY outcome

Timeframe: Baseline, Day 21 of Cycles 2, 4, and 6, Day 21 of Cycles 7, 8, 9, and 10, Day 21 of every other cycle, and at disease progression

Population: ITT population; only participants with an objective tumor response (CR or PR) were included in the analysis.

Duration of response is defined as time in months from the first documentation of objective tumor response (CR or PR) to objective tumor progression or death due to any cause. Participants without an event (documented progression or death) were censored at the date of last follow-up for progression. Duration of response was only calculated for participants who had a confirmed objective tumor response (CR or PR).

Outcome measures

Measure	Bevacizumab 7.5 mg Plus Chemotherapy n=56 Participants Cycles 1-6 (3-week cycles): Participants received bevacizumab 7.5 mg/kg IV on Day 1; either carboplatin at a dose required to achieve an AUC of 6 mg/mL IV and paclitaxel 200 mg/m\^2 IV on Day 1, or carboplatin at AUC 5 mg/mL IV on Day 1 and gemcitabine 1200 mg/m\^2 IV on Days 1 and 8. The choice of chemotherapy doublet, either carboplatin/paclitaxel or carboplatin/gemcitabine, was left to the discretion of the investigator. The cycle was repeated until disease progression or for a maximum of 6 cycles. Cycle 7 and beyond (3-week cycles): If the first 6 cycles were tolerated with no disease progression, participants then received bevacizumab 7.5 mg/kg IV on Day 1. This cycle was repeated every 3 weeks until disease progression.	Bevacizumab 15 mg Plus Chemotherapy n=65 Participants Cycles 1-6 (3-week cycles): Participants received bevacizumab 15 mg/kg IV on Day 1; either carboplatin at a dose required to achieve an AUC of 6 mg/mL IV and paclitaxel 200 mg/m\^2 IV on Day 1, or carboplatin at AUC 5 mg/mL IV on Day 1 and gemcitabine 1200 mg/m\^2 IV on Days 1 and 8. The choice of chemotherapy doublet, either carboplatin/paclitaxel or carboplatin/gemcitabine, was left to the discretion of the investigator. The cycle was repeated until disease progression or for a maximum of 6 cycles. Cycle 7 and beyond (3-week cycles): If the first 6 cycles were tolerated with no disease progression, participants then received bevacizumab 15 mg/kg IV on Day 1. This cycle was repeated every 3 weeks until disease progression.
Duration of Response - Percentage of Participants With an Event	80.4 percentage of participants	78.5 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Day 21 of Cycles 2, 4, and 6 (Bv + chemo), Day 21 of Cycles 7, 8, 9, and 10 (Bv), Day 21 of every other cycle (Bv), and at disease progression.

Population: ITT population: only participants with an objective tumor response (CR or PR) were included in the analysis.

The median time, in months, from the first documentation of objective tumor response (CR or PR) to objective tumor progression or death due to any cause. Participants without an event (documented progression or death) were censored at the date of last follow-up for progression. Duration of response was only calculated for participants who had a confirmed objective tumor response (CR or PR). Median Duration of Response was estimated using the Kaplan-Meier method.

Outcome measures

Measure	Bevacizumab 7.5 mg Plus Chemotherapy n=56 Participants Cycles 1-6 (3-week cycles): Participants received bevacizumab 7.5 mg/kg IV on Day 1; either carboplatin at a dose required to achieve an AUC of 6 mg/mL IV and paclitaxel 200 mg/m\^2 IV on Day 1, or carboplatin at AUC 5 mg/mL IV on Day 1 and gemcitabine 1200 mg/m\^2 IV on Days 1 and 8. The choice of chemotherapy doublet, either carboplatin/paclitaxel or carboplatin/gemcitabine, was left to the discretion of the investigator. The cycle was repeated until disease progression or for a maximum of 6 cycles. Cycle 7 and beyond (3-week cycles): If the first 6 cycles were tolerated with no disease progression, participants then received bevacizumab 7.5 mg/kg IV on Day 1. This cycle was repeated every 3 weeks until disease progression.	Bevacizumab 15 mg Plus Chemotherapy n=65 Participants Cycles 1-6 (3-week cycles): Participants received bevacizumab 15 mg/kg IV on Day 1; either carboplatin at a dose required to achieve an AUC of 6 mg/mL IV and paclitaxel 200 mg/m\^2 IV on Day 1, or carboplatin at AUC 5 mg/mL IV on Day 1 and gemcitabine 1200 mg/m\^2 IV on Days 1 and 8. The choice of chemotherapy doublet, either carboplatin/paclitaxel or carboplatin/gemcitabine, was left to the discretion of the investigator. The cycle was repeated until disease progression or for a maximum of 6 cycles. Cycle 7 and beyond (3-week cycles): If the first 6 cycles were tolerated with no disease progression, participants then received bevacizumab 15 mg/kg IV on Day 1. This cycle was repeated every 3 weeks until disease progression.
Duration of Response - Time to Event	5.8 months Interval 5.2 to 7.0	5.6 months Interval 4.6 to 7.1

SECONDARY outcome

Timeframe: Baseline, weekly to 28 days after last dose of study treatment, every 8 weeks thereafter to death due to any cause

Population: ITT population.

Overall survival was defined as the time between randomization and death due to any cause. Participants without an event were censored at the last time they were known to be alive. Overall Survival was estimated using the Kaplan-Meier method.

Outcome measures

Measure	Bevacizumab 7.5 mg Plus Chemotherapy n=154 Participants Cycles 1-6 (3-week cycles): Participants received bevacizumab 7.5 mg/kg IV on Day 1; either carboplatin at a dose required to achieve an AUC of 6 mg/mL IV and paclitaxel 200 mg/m\^2 IV on Day 1, or carboplatin at AUC 5 mg/mL IV on Day 1 and gemcitabine 1200 mg/m\^2 IV on Days 1 and 8. The choice of chemotherapy doublet, either carboplatin/paclitaxel or carboplatin/gemcitabine, was left to the discretion of the investigator. The cycle was repeated until disease progression or for a maximum of 6 cycles. Cycle 7 and beyond (3-week cycles): If the first 6 cycles were tolerated with no disease progression, participants then received bevacizumab 7.5 mg/kg IV on Day 1. This cycle was repeated every 3 weeks until disease progression.	Bevacizumab 15 mg Plus Chemotherapy n=149 Participants Cycles 1-6 (3-week cycles): Participants received bevacizumab 15 mg/kg IV on Day 1; either carboplatin at a dose required to achieve an AUC of 6 mg/mL IV and paclitaxel 200 mg/m\^2 IV on Day 1, or carboplatin at AUC 5 mg/mL IV on Day 1 and gemcitabine 1200 mg/m\^2 IV on Days 1 and 8. The choice of chemotherapy doublet, either carboplatin/paclitaxel or carboplatin/gemcitabine, was left to the discretion of the investigator. The cycle was repeated until disease progression or for a maximum of 6 cycles. Cycle 7 and beyond (3-week cycles): If the first 6 cycles were tolerated with no disease progression, participants then received bevacizumab 15 mg/kg IV on Day 1. This cycle was repeated every 3 weeks until disease progression.
Overall Survival - Percentage of Participants With an Event	64.3 percentage of participants	76.5 percentage of participants

SECONDARY outcome

Timeframe: Baseline, weekly to death due to any cause, or to end of study

Population: ITT Population.

Overall survival was defined as the time between randomization and death due to any cause. Participants without an event were censored at the last time they were known to be alive. Overall Survival was estimated using the Kaplan-Meier method.

Outcome measures

Measure	Bevacizumab 7.5 mg Plus Chemotherapy n=154 Participants Cycles 1-6 (3-week cycles): Participants received bevacizumab 7.5 mg/kg IV on Day 1; either carboplatin at a dose required to achieve an AUC of 6 mg/mL IV and paclitaxel 200 mg/m\^2 IV on Day 1, or carboplatin at AUC 5 mg/mL IV on Day 1 and gemcitabine 1200 mg/m\^2 IV on Days 1 and 8. The choice of chemotherapy doublet, either carboplatin/paclitaxel or carboplatin/gemcitabine, was left to the discretion of the investigator. The cycle was repeated until disease progression or for a maximum of 6 cycles. Cycle 7 and beyond (3-week cycles): If the first 6 cycles were tolerated with no disease progression, participants then received bevacizumab 7.5 mg/kg IV on Day 1. This cycle was repeated every 3 weeks until disease progression.	Bevacizumab 15 mg Plus Chemotherapy n=149 Participants Cycles 1-6 (3-week cycles): Participants received bevacizumab 15 mg/kg IV on Day 1; either carboplatin at a dose required to achieve an AUC of 6 mg/mL IV and paclitaxel 200 mg/m\^2 IV on Day 1, or carboplatin at AUC 5 mg/mL IV on Day 1 and gemcitabine 1200 mg/m\^2 IV on Days 1 and 8. The choice of chemotherapy doublet, either carboplatin/paclitaxel or carboplatin/gemcitabine, was left to the discretion of the investigator. The cycle was repeated until disease progression or for a maximum of 6 cycles. Cycle 7 and beyond (3-week cycles): If the first 6 cycles were tolerated with no disease progression, participants then received bevacizumab 15 mg/kg IV on Day 1. This cycle was repeated every 3 weeks until disease progression.
Overall Survival - Time to Event	13.4 months Interval 10.5 to 18.1	13.7 months Interval 11.4 to 17.0

Adverse Events

Bevacizumab 7.5 mg Plus Chemotherapy

Serious events: 53 serious events

Other events: 137 other events

Deaths: 0 deaths

Bevacizumab 15 mg Plus Chemotherapy

Serious events: 57 serious events

Other events: 132 other events

Deaths: 0 deaths

Serious adverse events

Measure	Bevacizumab 7.5 mg Plus Chemotherapy n=151 participants at risk Cycles 1-6 (3-week cycles): Participants received bevacizumab 7.5 mg/kg IV on Day 1; either carboplatin at a dose required to achieve an AUC of 6 mg/mL IV and paclitaxel 200 mg/m\^2 IV on Day 1, or carboplatin at AUC 5 mg/mL IV on Day 1 and gemcitabine 1200 mg/m\^2 IV on Days 1 and 8. The choice of chemotherapy doublet, either carboplatin/paclitaxel or carboplatin/gemcitabine, was left to the discretion of the investigator. The cycle was repeated until disease progression or for a maximum of 6 cycles. Cycle 7 and beyond (3-week cycles): If the first 6 cycles were tolerated with no disease progression, participants then received bevacizumab 7.5 mg/kg IV on Day 1. This cycle was repeated every 3 weeks until disease progression.	Bevacizumab 15 mg Plus Chemotherapy n=143 participants at risk Cycles 1-6 (3-week cycles): Participants received bevacizumab 15 mg/kg IV on Day 1; either carboplatin at a dose required to achieve an AUC of 6 mg/mL IV and paclitaxel 200 mg/m\^2 IV on Day 1, or carboplatin at AUC 5 mg/mL IV on Day 1 and gemcitabine 1200 mg/m\^2 IV on Days 1 and 8. The choice of chemotherapy doublet, either carboplatin/paclitaxel or carboplatin/gemcitabine, was left to the discretion of the investigator. The cycle was repeated until disease progression or for a maximum of 6 cycles. Cycle 7 and beyond (3-week cycles): If the first 6 cycles were tolerated with no disease progression, participants then received bevacizumab 15 mg/kg IV on Day 1. This cycle was repeated every 3 weeks until disease progression.
Blood and lymphatic system disorders Thrombocytopenia	7.9% 12/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	9.1% 13/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Blood and lymphatic system disorders Neutropenia	8.6% 13/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	4.9% 7/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Blood and lymphatic system disorders Anaemia	6.6% 10/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	5.6% 8/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Blood and lymphatic system disorders Granulocytopenia	2.0% 3/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	0.70% 1/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Blood and lymphatic system disorders Febrile Neutropenia	1.3% 2/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	0.70% 1/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Blood and lymphatic system disorders Leukopenia	1.3% 2/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	0.70% 1/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Blood and lymphatic system disorders Bone Marrow Failure	0.00% 0/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	0.70% 1/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Blood and lymphatic system disorders Pancytopenia	0.00% 0/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	0.70% 1/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Respiratory, thoracic and mediastinal disorders Pulmonary Embolism	0.66% 1/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	4.2% 6/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Respiratory, thoracic and mediastinal disorders Dyspnoea	1.3% 2/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	2.1% 3/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Respiratory, thoracic and mediastinal disorders Epistaxis	2.0% 3/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	0.70% 1/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Respiratory, thoracic and mediastinal disorders Chronic Obstructive Pulmonary Disease	0.66% 1/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	0.70% 1/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	1.4% 2/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Respiratory, thoracic and mediastinal disorders Bronchitis Chronic	0.66% 1/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	0.00% 0/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.66% 1/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	0.00% 0/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Respiratory, thoracic and mediastinal disorders Pleural Effusion	0.66% 1/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	0.00% 0/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Respiratory, thoracic and mediastinal disorders Pulmonary Artery Thrombosis	0.00% 0/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	0.70% 1/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Respiratory, thoracic and mediastinal disorders Pulmonary Haemorrhage	0.66% 1/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	0.00% 0/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Respiratory, thoracic and mediastinal disorders Respiratory Failure	0.66% 1/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	0.00% 0/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Infections and infestations Pneumonia	3.3% 5/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	4.9% 7/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Infections and infestations Pyothorax	0.66% 1/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	0.70% 1/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Infections and infestations Sepsis	0.00% 0/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	1.4% 2/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Infections and infestations Appendicitis	0.66% 1/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	0.00% 0/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Infections and infestations Bronchopneumonia	0.00% 0/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	0.70% 1/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Infections and infestations Infection	0.00% 0/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	0.70% 1/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Infections and infestations Localised Infection	0.00% 0/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	0.70% 1/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Infections and infestations Lung Infection	0.66% 1/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	0.00% 0/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Infections and infestations Neutropenic Sepsis	0.00% 0/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	0.70% 1/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Infections and infestations Pneumonia Legionella	0.00% 0/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	0.70% 1/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Infections and infestations Pseudomonal Sepsis	0.66% 1/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	0.00% 0/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Infections and infestations Pulmonary Tuberculosis	0.00% 0/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	0.70% 1/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
General disorders Pyrexia	0.66% 1/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	3.5% 5/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
General disorders Death	0.66% 1/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	0.70% 1/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
General disorders Asthenia	0.00% 0/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	0.70% 1/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
General disorders Chest Pain	0.66% 1/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	0.00% 0/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
General disorders Fatigue	0.00% 0/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	0.70% 1/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Nervous system disorders Cerebral Infarction	0.66% 1/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	0.70% 1/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Nervous system disorders Cerebrovascular Accident	0.66% 1/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	0.70% 1/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Nervous system disorders Neuropathy Peripheral	0.66% 1/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	0.70% 1/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Nervous system disorders Embolic Stroke	0.00% 0/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	0.70% 1/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Nervous system disorders Ischaemic Stoke	0.00% 0/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	0.70% 1/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Nervous system disorders Syncope	0.66% 1/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	0.00% 0/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Cardiac disorders Cardiac Failure	0.00% 0/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	1.4% 2/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Cardiac disorders Myocardial Infarction	1.3% 2/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	0.00% 0/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Cardiac disorders Angina Pectoris	0.66% 1/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	0.00% 0/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Cardiac disorders Left Ventricular Failure	0.66% 1/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	0.00% 0/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Cardiac disorders Palapitations	0.66% 1/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	0.00% 0/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Cardiac disorders Tachycardia Paroxysmal	0.66% 1/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	0.00% 0/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Gastrointestinal disorders Constipation	0.00% 0/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	0.70% 1/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Gastrointestinal disorders Diarrhoea	0.00% 0/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	0.70% 1/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Gastrointestinal disorders Gastric Ulcer	0.66% 1/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	0.00% 0/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Gastrointestinal disorders Intestinal Perforation	0.00% 0/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	0.70% 1/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Gastrointestinal disorders Melaena	0.66% 1/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	0.00% 0/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Gastrointestinal disorders Nausea	0.00% 0/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	0.70% 1/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Gastrointestinal disorders Rectal Haemorrhage	0.66% 1/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	0.00% 0/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Gastrointestinal disorders Vomiting	0.00% 0/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	0.70% 1/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Vascular disorders Deep Vein Thrombosis	0.66% 1/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	0.70% 1/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Vascular disorders Hypertensive Crisis	0.66% 1/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	0.70% 1/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Vascular disorders Arterial Thrombosis	0.00% 0/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	0.70% 1/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Injury, poisoning and procedural complications Femur Fracture	0.00% 0/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	0.70% 1/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Injury, poisoning and procedural complications Intestinal Anastomosis Complication	0.00% 0/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	0.70% 1/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Injury, poisoning and procedural complications Rib Fracture	0.00% 0/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	0.70% 1/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Injury, poisoning and procedural complications Wound Dehiscence	0.00% 0/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	0.70% 1/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Metabolism and nutrition disorders Fluid Retension	0.00% 0/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	0.70% 1/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Metabolism and nutrition disorders Hypercalcaemia	0.00% 0/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	0.70% 1/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	0.70% 1/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Metabolism and nutrition disorders Hyponatraemia	0.66% 1/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	0.00% 0/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast Cancer	0.00% 0/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	0.70% 1/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cancer Pain	0.66% 1/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	0.00% 0/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasm	0.00% 0/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	0.70% 1/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Renal and urinary disorders Renal Failure	0.66% 1/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	0.00% 0/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Renal and urinary disorders Urinary Tract Obstruction	0.66% 1/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	0.00% 0/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Immune system disorders Hypersensitivity	0.00% 0/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	0.70% 1/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Investigations Renal Scan Abnormal	0.66% 1/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	0.00% 0/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Musculoskeletal and connective tissue disorders Musculoskeletal Pain	0.00% 0/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	0.70% 1/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.

Other adverse events

Measure	Bevacizumab 7.5 mg Plus Chemotherapy n=151 participants at risk Cycles 1-6 (3-week cycles): Participants received bevacizumab 7.5 mg/kg IV on Day 1; either carboplatin at a dose required to achieve an AUC of 6 mg/mL IV and paclitaxel 200 mg/m\^2 IV on Day 1, or carboplatin at AUC 5 mg/mL IV on Day 1 and gemcitabine 1200 mg/m\^2 IV on Days 1 and 8. The choice of chemotherapy doublet, either carboplatin/paclitaxel or carboplatin/gemcitabine, was left to the discretion of the investigator. The cycle was repeated until disease progression or for a maximum of 6 cycles. Cycle 7 and beyond (3-week cycles): If the first 6 cycles were tolerated with no disease progression, participants then received bevacizumab 7.5 mg/kg IV on Day 1. This cycle was repeated every 3 weeks until disease progression.	Bevacizumab 15 mg Plus Chemotherapy n=143 participants at risk Cycles 1-6 (3-week cycles): Participants received bevacizumab 15 mg/kg IV on Day 1; either carboplatin at a dose required to achieve an AUC of 6 mg/mL IV and paclitaxel 200 mg/m\^2 IV on Day 1, or carboplatin at AUC 5 mg/mL IV on Day 1 and gemcitabine 1200 mg/m\^2 IV on Days 1 and 8. The choice of chemotherapy doublet, either carboplatin/paclitaxel or carboplatin/gemcitabine, was left to the discretion of the investigator. The cycle was repeated until disease progression or for a maximum of 6 cycles. Cycle 7 and beyond (3-week cycles): If the first 6 cycles were tolerated with no disease progression, participants then received bevacizumab 15 mg/kg IV on Day 1. This cycle was repeated every 3 weeks until disease progression.
Blood and lymphatic system disorders Neutropenia	47.7% 72/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	39.9% 57/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Blood and lymphatic system disorders Thrombocytopenia	41.1% 62/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	28.7% 41/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Blood and lymphatic system disorders Anaemia	35.8% 54/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	27.3% 39/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Blood and lymphatic system disorders Leukopenia	18.5% 28/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	11.2% 16/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Gastrointestinal disorders Nausea	34.4% 52/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	26.6% 38/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Gastrointestinal disorders Constipation	17.9% 27/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	14.0% 20/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Gastrointestinal disorders Vomiting	11.9% 18/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	15.4% 22/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Gastrointestinal disorders Diarrhoea	12.6% 19/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	11.2% 16/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Gastrointestinal disorders Stomatitis	6.0% 9/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	6.3% 9/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Gastrointestinal disorders Mouth ulceration	7.9% 12/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	3.5% 5/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Gastrointestinal disorders Abdominal pain upper	6.6% 10/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	3.5% 5/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Respiratory, thoracic and mediastinal disorders Epistaxis	21.9% 33/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	25.9% 37/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Respiratory, thoracic and mediastinal disorders Cough	16.6% 25/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	12.6% 18/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Respiratory, thoracic and mediastinal disorders Dyspnoea	7.9% 12/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	15.4% 22/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	7.3% 11/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	8.4% 12/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	6.0% 9/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	8.4% 12/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Respiratory, thoracic and mediastinal disorders Haemoptysis	6.0% 9/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	5.6% 8/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Respiratory, thoracic and mediastinal disorders Dysphonia	6.6% 10/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	2.8% 4/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
General disorders Fatigue	31.1% 47/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	28.7% 41/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
General disorders Chest pain	12.6% 19/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	6.3% 9/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
General disorders Pyrexia	11.3% 17/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	4.9% 7/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
General disorders Asthenia	8.6% 13/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	7.0% 10/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
General disorders Mucosal inflammation	6.6% 10/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	6.3% 9/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Nervous system disorders Dizziness	11.3% 17/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	11.2% 16/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Nervous system disorders Neuropathy peripheral	12.6% 19/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	7.0% 10/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Nervous system disorders Headache	10.6% 16/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	8.4% 12/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Nervous system disorders Dysgeusia	6.6% 10/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	5.6% 8/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Nervous system disorders Polyneuropathy	3.3% 5/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	5.6% 8/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Skin and subcutaneous tissue disorders Alopecia	23.2% 35/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	21.0% 30/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Skin and subcutaneous tissue disorders Rash	9.9% 15/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	7.7% 11/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Skin and subcutaneous tissue disorders Pruritus	6.0% 9/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	4.2% 6/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Musculoskeletal and connective tissue disorders Arthralgia	13.9% 21/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	10.5% 15/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Musculoskeletal and connective tissue disorders Back pain	8.6% 13/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	9.1% 13/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	9.9% 15/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	4.2% 6/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Musculoskeletal and connective tissue disorders Pain in extremity	7.3% 11/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	4.9% 7/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Vascular disorders Hypertension	17.9% 27/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	21.0% 30/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Metabolism and nutrition disorders Decreased appetite	10.6% 16/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	18.2% 26/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Investigations Weight decreased	9.3% 14/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	9.1% 13/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Investigations Alanine aminotransferase increased	6.0% 9/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	2.8% 4/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Infections and infestations Nasopharyngitis	9.3% 14/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	9.1% 13/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Infections and infestations Urinary tract infection	5.3% 8/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	5.6% 8/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Renal and urinary disorders Proteinuria	7.9% 12/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	11.9% 17/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.
Psychiatric disorders Insomnia	7.9% 12/151 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.	6.3% 9/143 • Adverse events were assessed from first study treatment until 28 days after last study treatment (LST). In addition, surgical procedures, major injuries and adverse events of special interest for bevacizumab were assessed to at least 6 months after LST.

Additional Information

Medical Communications

Hoffmann-LaRoche

Phone: 800-821-8590

Email: genentech@druginfo.com

Results disclosure agreements

• Principal investigator is a sponsor employee The study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
• Publication restrictions are in place

Restriction type: OTHER