A Study of Avastin (Bevacizumab) in Combination With Carb... | NCT00700180

ID	Type	Description	Link
2008-000662-23

Label	Type	Description	Intervention Names
1	Experimental		Drug: bevacizumab [Avastin] Drug: Carboplatin-based chemotherapy
2	Experimental		Drug: bevacizumab [Avastin] Drug: Carboplatin-based chemotherapy

Name	Type	Description	Arm Group Labels	Other Names
bevacizumab [Avastin]	Drug	7.5mg/kg iv on day 1 of each 3 week cycle	1

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Percentage of Participants With a Best Overall Response of Complete Response (CR) or Partial Response (PR) by Dichotomized Baseline Plasma Marker Level	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	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.

Secondary Outcomes

Measure	Description	Time Frame
Progression-Free Survival - Percentage of Participants With an Event	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.

Name	Affiliation	Role
Clinical Trials	Hoffmann-La Roche	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
		St Leonards	New South Wales	2065	Australia

ID	Title	Description
FG000	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.

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Percentage of Participants With a Best Overall Response of Complete Response (CR) or Partial Response (PR) by Dichotomized Baseline Plasma Marker Level

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

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.

Number

percentage of participants

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.

ID	Title	Description
OG000	Bevacizumab 7.5 mg Plus Chemotherapy	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.
OG001	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.

Units	Counts
Participants	OG00082 OG00175

Title

Denominators

Categories

bFGF low level (n=77,65)

Title	Measurements
	OG00042.86 OG00147.69

bFGF high level (n=66,75)

Title	Measurements
	OG000

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000	bFGF (high versus low)	Regression, Logistic		0.8127	Multiple logistic regression model with treatment, biomarker level (dichotomized) and baseline prognostic factors as covariates.	Odds Ratio (OR)	1.07			2-Sided	95	0.63	1.80				No	Superiority or Other
OG000

Secondary

Progression-Free Survival - Percentage of Participants With an Event

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.

ITT population.

Number

percentage of participants

Baseline, Day 1, weekly to disease progression

ID	Title	Description
OG000	Bevacizumab 7.5 mg Plus Chemotherapy	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.

Secondary

Progression-Free Survival - Time to Event

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.

ITT Population.

Median

95% Confidence Interval

months

Baseline, Day 1, weekly to disease progression

ID	Title	Description
OG000	Bevacizumab 7.5 mg Plus Chemotherapy	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.
OG001	Bevacizumab 15 mg Plus Chemotherapy

Secondary

Percentage of Participants With Objective Response

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.

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.

Number

95% Confidence Interval

percentage of participants

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

ID	Title	Description
OG000	Bevacizumab 7.5 mg Plus Chemotherapy	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.

Secondary

Percentage of Participants With Measurable Disease at Baseline Who Achieved CR, PR, or Stable Disease (SD) for at Least 6 Weeks

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.

ITT Population

Number

95% Confidence Interval

percentage of participants

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

ID	Title	Description
OG000	Bevacizumab 7.5 mg Plus Chemotherapy	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.

Secondary

Duration of Response - Percentage of Participants With an Event

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).

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

Number

percentage of participants

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

ID	Title	Description
OG000	Bevacizumab 7.5 mg Plus Chemotherapy	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.
OG001	Bevacizumab 15 mg Plus Chemotherapy

Secondary

Duration of Response - Time to Event

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.

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

Median

95% Confidence Interval

months

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.

ID	Title	Description
OG000	Bevacizumab 7.5 mg Plus Chemotherapy	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.
OG001

Secondary

Overall Survival - Percentage of Participants With an Event

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.

ITT population.

Number

percentage of participants

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

ID	Title	Description
OG000	Bevacizumab 7.5 mg Plus Chemotherapy	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.
OG001	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.

Secondary

Overall Survival - Time to Event

ITT Population.

Median

95% Confidence Interval

months

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

ID	Title	Description
OG000	Bevacizumab 7.5 mg Plus Chemotherapy	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.
OG001	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.

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 14.0	Non-systematic Assessment	EG00012 affected151 at risk EG00113 affected143 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 14.0	Non-systematic Assessment	EG00013 affected151 at risk EG0017 affected143 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA 14.0	Non-systematic Assessment	EG00010 affected151 at risk EG0018 affected143 at risk
Granulocytopenia	Blood and lymphatic system disorders	MedDRA 14.0	Non-systematic Assessment	EG0003 affected151 at risk EG0011 affected143 at risk
Febrile Neutropenia	Blood and lymphatic system disorders	MedDRA 14.0	Non-systematic Assessment	EG0002 affected151 at risk EG0011 affected143 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA 14.0	Non-systematic Assessment	EG0002 affected151 at risk EG0011 affected143 at risk
Bone Marrow Failure	Blood and lymphatic system disorders	MedDRA 14.0	Non-systematic Assessment	EG0000 affected151 at risk EG0011 affected143 at risk
Pancytopenia	Blood and lymphatic system disorders	MedDRA 14.0	Non-systematic Assessment	EG0000 affected151 at risk EG0011 affected143 at risk
Pulmonary Embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected151 at risk EG0016 affected143 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Non-systematic Assessment	EG0002 affected151 at risk EG0013 affected143 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Non-systematic Assessment	EG0003 affected151 at risk EG0011 affected143 at risk
Chronic Obstructive Pulmonary Disease	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected151 at risk EG0011 affected143 at risk
Pneumothorax	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Non-systematic Assessment	EG0000 affected151 at risk EG0012 affected143 at risk
Bronchitis Chronic	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected151 at risk EG0010 affected143 at risk
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected151 at risk EG0010 affected143 at risk
Pleural Effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected151 at risk EG0010 affected143 at risk
Pulmonary Artery Thrombosis	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Non-systematic Assessment	EG0000 affected151 at risk EG0011 affected143 at risk
Pulmonary Haemorrhage	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected151 at risk EG0010 affected143 at risk
Respiratory Failure	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected151 at risk EG0010 affected143 at risk
Pneumonia	Infections and infestations	MedDRA 14.0	Non-systematic Assessment	EG0005 affected151 at risk EG0017 affected143 at risk
Pyothorax	Infections and infestations	MedDRA 14.0	Non-systematic Assessment	EG0001 affected151 at risk EG0011 affected143 at risk
Sepsis	Infections and infestations	MedDRA 14.0	Non-systematic Assessment	EG0000 affected151 at risk EG0012 affected143 at risk
Appendicitis	Infections and infestations	MedDRA 14.0	Non-systematic Assessment	EG0001 affected151 at risk EG0010 affected143 at risk
Bronchopneumonia	Infections and infestations	MedDRA 14.0	Non-systematic Assessment	EG0000 affected151 at risk EG0011 affected143 at risk
Infection	Infections and infestations	MedDRA 14.0	Non-systematic Assessment	EG0000 affected151 at risk EG0011 affected143 at risk
Localised Infection	Infections and infestations	MedDRA 14.0	Non-systematic Assessment	EG0000 affected151 at risk EG0011 affected143 at risk
Lung Infection	Infections and infestations	MedDRA 14.0	Non-systematic Assessment	EG0001 affected151 at risk EG0010 affected143 at risk
Neutropenic Sepsis	Infections and infestations	MedDRA 14.0	Non-systematic Assessment	EG0000 affected151 at risk EG0011 affected143 at risk
Pneumonia Legionella	Infections and infestations	MedDRA 14.0	Non-systematic Assessment	EG0000 affected151 at risk EG0011 affected143 at risk
Pseudomonal Sepsis	Infections and infestations	MedDRA 14.0	Non-systematic Assessment	EG0001 affected151 at risk EG0010 affected143 at risk
Pulmonary Tuberculosis	Infections and infestations	MedDRA 14.0	Non-systematic Assessment	EG0000 affected151 at risk EG0011 affected143 at risk
Pyrexia	General disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected151 at risk EG0015 affected143 at risk
Death	General disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected151 at risk EG0011 affected143 at risk
Asthenia	General disorders	MedDRA 14.0	Non-systematic Assessment	EG0000 affected151 at risk EG0011 affected143 at risk
Chest Pain	General disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected151 at risk EG0010 affected143 at risk
Fatigue	General disorders	MedDRA 14.0	Non-systematic Assessment	EG0000 affected151 at risk EG0011 affected143 at risk
Cerebral Infarction	Nervous system disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected151 at risk EG0011 affected143 at risk
Cerebrovascular Accident	Nervous system disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected151 at risk EG0011 affected143 at risk
Neuropathy Peripheral	Nervous system disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected151 at risk EG0011 affected143 at risk
Embolic Stroke	Nervous system disorders	MedDRA 14.0	Non-systematic Assessment	EG0000 affected151 at risk EG0011 affected143 at risk
Ischaemic Stoke	Nervous system disorders	MedDRA 14.0	Non-systematic Assessment	EG0000 affected151 at risk EG0011 affected143 at risk
Syncope	Nervous system disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected151 at risk EG0010 affected143 at risk
Cardiac Failure	Cardiac disorders	MedDRA 14.0	Non-systematic Assessment	EG0000 affected151 at risk EG0012 affected143 at risk
Myocardial Infarction	Cardiac disorders	MedDRA 14.0	Non-systematic Assessment	EG0002 affected151 at risk EG0010 affected143 at risk
Angina Pectoris	Cardiac disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected151 at risk EG0010 affected143 at risk
Left Ventricular Failure	Cardiac disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected151 at risk EG0010 affected143 at risk
Palapitations	Cardiac disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected151 at risk EG0010 affected143 at risk
Tachycardia Paroxysmal	Cardiac disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected151 at risk EG0010 affected143 at risk
Constipation	Gastrointestinal disorders	MedDRA 14.0	Non-systematic Assessment	EG0000 affected151 at risk EG0011 affected143 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 14.0	Non-systematic Assessment	EG0000 affected151 at risk EG0011 affected143 at risk
Gastric Ulcer	Gastrointestinal disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected151 at risk EG0010 affected143 at risk
Intestinal Perforation	Gastrointestinal disorders	MedDRA 14.0	Non-systematic Assessment	EG0000 affected151 at risk EG0011 affected143 at risk
Melaena	Gastrointestinal disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected151 at risk EG0010 affected143 at risk
Nausea	Gastrointestinal disorders	MedDRA 14.0	Non-systematic Assessment	EG0000 affected151 at risk EG0011 affected143 at risk
Rectal Haemorrhage	Gastrointestinal disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected151 at risk EG0010 affected143 at risk
Vomiting	Gastrointestinal disorders	MedDRA 14.0	Non-systematic Assessment	EG0000 affected151 at risk EG0011 affected143 at risk
Deep Vein Thrombosis	Vascular disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected151 at risk EG0011 affected143 at risk
Hypertensive Crisis	Vascular disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected151 at risk EG0011 affected143 at risk
Arterial Thrombosis	Vascular disorders	MedDRA 14.0	Non-systematic Assessment	EG0000 affected151 at risk EG0011 affected143 at risk
Femur Fracture	Injury, poisoning and procedural complications	MedDRA 14.0	Non-systematic Assessment	EG0000 affected151 at risk EG0011 affected143 at risk
Intestinal Anastomosis Complication	Injury, poisoning and procedural complications	MedDRA 14.0	Non-systematic Assessment	EG0000 affected151 at risk EG0011 affected143 at risk
Rib Fracture	Injury, poisoning and procedural complications	MedDRA 14.0	Non-systematic Assessment	EG0000 affected151 at risk EG0011 affected143 at risk
Wound Dehiscence	Injury, poisoning and procedural complications	MedDRA 14.0	Non-systematic Assessment	EG0000 affected151 at risk EG0011 affected143 at risk
Fluid Retension	Metabolism and nutrition disorders	MedDRA 14.0	Non-systematic Assessment	EG0000 affected151 at risk EG0011 affected143 at risk
Hypercalcaemia	Metabolism and nutrition disorders	MedDRA 14.0	Non-systematic Assessment	EG0000 affected151 at risk EG0011 affected143 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 14.0	Non-systematic Assessment	EG0000 affected151 at risk EG0011 affected143 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected151 at risk EG0010 affected143 at risk
Breast Cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 14.0	Non-systematic Assessment	EG0000 affected151 at risk EG0011 affected143 at risk
Cancer Pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 14.0	Non-systematic Assessment	EG0001 affected151 at risk EG0010 affected143 at risk
Neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 14.0	Non-systematic Assessment	EG0000 affected151 at risk EG0011 affected143 at risk
Renal Failure	Renal and urinary disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected151 at risk EG0010 affected143 at risk
Urinary Tract Obstruction	Renal and urinary disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected151 at risk EG0010 affected143 at risk
Hypersensitivity	Immune system disorders	MedDRA 14.0	Non-systematic Assessment	EG0000 affected151 at risk EG0011 affected143 at risk
Renal Scan Abnormal	Investigations	MedDRA 14.0	Non-systematic Assessment	EG0001 affected151 at risk EG0010 affected143 at risk
Musculoskeletal Pain	Musculoskeletal and connective tissue disorders	MedDRA 14.0	Non-systematic Assessment	EG0000 affected151 at risk EG0011 affected143 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Neutropenia	Blood and lymphatic system disorders	MedDRA 14.0	Non-systematic Assessment	EG00072 affected151 at risk EG00157 affected143 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 14.0	Non-systematic Assessment	EG00062 affected151 at risk EG00141 affected143 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA 14.0	Non-systematic Assessment	EG00054 affected151 at risk EG00139 affected143 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA 14.0	Non-systematic Assessment	EG00028 affected151 at risk EG00116 affected143 at risk
Nausea	Gastrointestinal disorders	MedDRA 14.0	Non-systematic Assessment	EG00052 affected151 at risk EG00138 affected143 at risk
Constipation	Gastrointestinal disorders	MedDRA 14.0	Non-systematic Assessment	EG00027 affected151 at risk EG00120 affected143 at risk
Vomiting	Gastrointestinal disorders	MedDRA 14.0	Non-systematic Assessment	EG00018 affected151 at risk EG00122 affected143 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 14.0	Non-systematic Assessment	EG00019 affected151 at risk EG00116 affected143 at risk
Stomatitis	Gastrointestinal disorders	MedDRA 14.0	Non-systematic Assessment	EG0009 affected151 at risk EG0019 affected143 at risk
Mouth ulceration	Gastrointestinal disorders	MedDRA 14.0	Non-systematic Assessment	EG00012 affected151 at risk EG0015 affected143 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 14.0	Non-systematic Assessment	EG00010 affected151 at risk EG0015 affected143 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Non-systematic Assessment	EG00033 affected151 at risk EG00137 affected143 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Non-systematic Assessment	EG00025 affected151 at risk EG00118 affected143 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Non-systematic Assessment	EG00012 affected151 at risk EG00122 affected143 at risk
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Non-systematic Assessment	EG00011 affected151 at risk EG00112 affected143 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Non-systematic Assessment	EG0009 affected151 at risk EG00112 affected143 at risk
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Non-systematic Assessment	EG0009 affected151 at risk EG0018 affected143 at risk
Dysphonia	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Non-systematic Assessment	EG00010 affected151 at risk EG0014 affected143 at risk
Fatigue	General disorders	MedDRA 14.0	Non-systematic Assessment	EG00047 affected151 at risk EG00141 affected143 at risk
Chest pain	General disorders	MedDRA 14.0	Non-systematic Assessment	EG00019 affected151 at risk EG0019 affected143 at risk
Pyrexia	General disorders	MedDRA 14.0	Non-systematic Assessment	EG00017 affected151 at risk EG0017 affected143 at risk
Asthenia	General disorders	MedDRA 14.0	Non-systematic Assessment	EG00013 affected151 at risk EG00110 affected143 at risk
Mucosal inflammation	General disorders	MedDRA 14.0	Non-systematic Assessment	EG00010 affected151 at risk EG0019 affected143 at risk
Dizziness	Nervous system disorders	MedDRA 14.0	Non-systematic Assessment	EG00017 affected151 at risk EG00116 affected143 at risk
Neuropathy peripheral	Nervous system disorders	MedDRA 14.0	Non-systematic Assessment	EG00019 affected151 at risk EG00110 affected143 at risk
Headache	Nervous system disorders	MedDRA 14.0	Non-systematic Assessment	EG00016 affected151 at risk EG00112 affected143 at risk
Dysgeusia	Nervous system disorders	MedDRA 14.0	Non-systematic Assessment	EG00010 affected151 at risk EG0018 affected143 at risk
Polyneuropathy	Nervous system disorders	MedDRA 14.0	Non-systematic Assessment	EG0005 affected151 at risk EG0018 affected143 at risk
Alopecia	Skin and subcutaneous tissue disorders	MedDRA 14.0	Non-systematic Assessment	EG00035 affected151 at risk EG00130 affected143 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 14.0	Non-systematic Assessment	EG00015 affected151 at risk EG00111 affected143 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 14.0	Non-systematic Assessment	EG0009 affected151 at risk EG0016 affected143 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 14.0	Non-systematic Assessment	EG00021 affected151 at risk EG00115 affected143 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 14.0	Non-systematic Assessment	EG00013 affected151 at risk EG00113 affected143 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA 14.0	Non-systematic Assessment	EG00015 affected151 at risk EG0016 affected143 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 14.0	Non-systematic Assessment	EG00011 affected151 at risk EG0017 affected143 at risk
Hypertension	Vascular disorders	MedDRA 14.0	Non-systematic Assessment	EG00027 affected151 at risk EG00130 affected143 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 14.0	Non-systematic Assessment	EG00016 affected151 at risk EG00126 affected143 at risk
Weight decreased	Investigations	MedDRA 14.0	Non-systematic Assessment	EG00014 affected151 at risk EG00113 affected143 at risk
Alanine aminotransferase increased	Investigations	MedDRA 14.0	Non-systematic Assessment	EG0009 affected151 at risk EG0014 affected143 at risk
Nasopharyngitis	Infections and infestations	MedDRA 14.0	Non-systematic Assessment	EG00014 affected151 at risk EG00113 affected143 at risk
Urinary tract infection	Infections and infestations	MedDRA 14.0	Non-systematic Assessment	EG0008 affected151 at risk EG0018 affected143 at risk
Proteinuria	Renal and urinary disorders	MedDRA 14.0	Non-systematic Assessment	EG00012 affected151 at risk EG00117 affected143 at risk
Insomnia	Psychiatric disorders	MedDRA 14.0	Non-systematic Assessment	EG00012 affected151 at risk EG0019 affected143 at risk

ID	Term
D002283	Carcinoma, Bronchogenic
D001984	Bronchial Neoplasms
D008175	Lung Neoplasms
D012142	Respiratory Tract Neoplasms
D013899	Thoracic Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D008171	Lung Diseases
D012140	Respiratory Tract Diseases

ID	Term
D061067	Antibodies, Monoclonal, Humanized
D000911	Antibodies, Monoclonal
D000906	Antibodies
D007136	Immunoglobulins
D007162	Immunoproteins
D001798	Blood Proteins
D011506	Proteins
D000602	Amino Acids, Peptides, and Proteins
D012712	Serum Globulins
D005916	Globulins

ID	Title	Description
BG000	Bevacizumab 7.5 mg Plus Chemotherapy	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.
BG001	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.
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Bevacizumab 7.5 mg Plus Chemotherapy	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.			53	151	137	151
EG001	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.			57	143	132	143