Trial Outcomes & Findings for A Study Comparing Bevacizumab Therapy With or Without Erlotinib for First-Line Treatment of Non-Small Cell Lung Cancer (ATLAS) (NCT NCT00257608)

Last Updated: 2016-04-18

Results Overview

PFS was defined as the length of time from randomization until documented disease progression or death from any cause, whichever occurred earlier. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Data presented until cut-off date 18 July 2008.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1145 participants

Primary outcome timeframe

Approximately 3 years

Results posted on

2016-04-18

Participant Flow

This study was conducted in 14 countries between 10 January 2006 and 19 June 2009.

Participant milestones

Participant milestones
Measure	Bevacizumab + Chemotherapy Participants received one of six chemotherapy regimens (Carboplatin + Paclitaxel or Carboplatin + Gemcitabine or Carboplatin + Docetaxel or Cisplatin + Gemcitabine or Cisplatin + Docetaxel / Cisplatin + vinorelbine) followed by Bevacizumab on Day 1 of each cycle up to 4 cycles.	Bevacizumab + Placebo Participants who completed four cycles of chemotherapy + bevacizumab received Bevacizumab 15 milligram per kilogram (mg/kg) intravenously (IV) on Day 1 of every 21-day cycle along with matched Placebo to Erlotinib orally daily.	Bevacizumab + Erlotinib Participants who completed four cycles of chemotherapy + bevacizumab received received IV dose of Bevacizumab 15 mg/kg on Day 1 of every 21-day cycle along with Erlotinib as 150 mg per day orally daily.
Chemotherapy Phase STARTED	1145	0	0
Chemotherapy Phase COMPLETED	769	0	0
Chemotherapy Phase NOT COMPLETED	376	0	0
Post Chemotherapy Phase STARTED	0	373	370
Post Chemotherapy Phase COMPLETED	0	109	126
Post Chemotherapy Phase NOT COMPLETED	0	264	244

Reasons for withdrawal

Reasons for withdrawal
Measure	Bevacizumab + Chemotherapy Participants received one of six chemotherapy regimens (Carboplatin + Paclitaxel or Carboplatin + Gemcitabine or Carboplatin + Docetaxel or Cisplatin + Gemcitabine or Cisplatin + Docetaxel / Cisplatin + vinorelbine) followed by Bevacizumab on Day 1 of each cycle up to 4 cycles.	Bevacizumab + Placebo Participants who completed four cycles of chemotherapy + bevacizumab received Bevacizumab 15 milligram per kilogram (mg/kg) intravenously (IV) on Day 1 of every 21-day cycle along with matched Placebo to Erlotinib orally daily.	Bevacizumab + Erlotinib Participants who completed four cycles of chemotherapy + bevacizumab received received IV dose of Bevacizumab 15 mg/kg on Day 1 of every 21-day cycle along with Erlotinib as 150 mg per day orally daily.
Chemotherapy Phase Adverse Event	138	0	0
Chemotherapy Phase Disease progression	139	0	0
Chemotherapy Phase Unwillingness or inability to comply	6	0	0
Chemotherapy Phase Need for concomitant/ancillary therapy	27	0	0
Chemotherapy Phase Patient's decision to discontinue	35	0	0
Chemotherapy Phase Unrelated intercurrent illness	3	0	0
Chemotherapy Phase Physician Decision	28	0	0
Post Chemotherapy Phase Adverse Event	0	34	38
Post Chemotherapy Phase Disease progression	0	204	168
Post Chemotherapy Phase Unwillingness or inability to comply	0	4	5
Post Chemotherapy Phase Need for concomitant/ancillary therapy	0	5	5
Post Chemotherapy Phase Patient's decision to discontinue	0	4	8
Post Chemotherapy Phase Unrelated intercurrent illness	0	0	1
Post Chemotherapy Phase Lost to Follow-up	0	0	1
Post Chemotherapy Phase Physician Decision	0	8	11
Post Chemotherapy Phase Sponsor's decision to terminate study	0	1	0
Post Chemotherapy Phase Not treated	0	4	7

Baseline Characteristics

A Study Comparing Bevacizumab Therapy With or Without Erlotinib for First-Line Treatment of Non-Small Cell Lung Cancer (ATLAS)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Bevacizumab + Placebo n=373 Participants Participants received Bevacizumab 15 milligram per kilogram (mg/kg) intravenously (IV) on Day 1 of every 21-day cycle along with matched Placebo to Erlotinib orally daily	Bevacizumab + Erlotinib n=370 Participants Participants received Bevacizumab 15 mg/kg IV on Day 1 of every 21-day cycle along with Erlotinib as 150 mg per day orally daily	Total n=743 Participants Total of all reporting groups
Age, Continuous	62.8 Years STANDARD_DEVIATION 10.8 • n=99 Participants	62.9 Years STANDARD_DEVIATION 10.3 • n=107 Participants	62.9 Years STANDARD_DEVIATION 10.6 • n=206 Participants
Sex: Female, Male Female	177 Participants n=99 Participants	177 Participants n=107 Participants	354 Participants n=206 Participants
Sex: Female, Male Male	196 Participants n=99 Participants	193 Participants n=107 Participants	389 Participants n=206 Participants

PRIMARY outcome

Timeframe: Approximately 3 years

Population: Intent to treat (ITT) population included all participants who were randomized during the post-chemotherapy phase.

Outcome measures

Outcome measures
Measure	Bevacizumab + Placebo n=373 Participants Participants who completed four cycles of chemotherapy + bevacizumab received Bevacizumab 15 milligram per kilogram (mg/kg) intravenously (IV) on Day 1 of every 21-day cycle along with matched Placebo to Erlotinib orally daily.	Bevacizumab + Erlotinib n=370 Participants Participants who completed four cycles of chemotherapy + bevacizumab received received IV dose of Bevacizumab 15 mg/kg on Day 1 of every 21-day cycle along with Erlotinib as 150 mg per day orally daily.	Carboplatin + Docetaxel Participants received IV dose of Carboplatin at a dose based on the AUC of of 6 mg/mL × min and Docetaxel 75 mg/m\^2, respectively followed by Bevacizumab on Day 1 of each 21-day cycle up to 4 cycles.	Cisplatin + Gemcitabine Participants received IV dose of Cisplatin 80 mg/m\^2 on Day 1 of each 21-day cycle and Gemcitabine 1000-1250 mg/m\^2 on Day 1 and Day 8 followed by Bevacizumab of each 21-day cycle up to 4 cycles.	Other Included participants who received Cisplatin + Docetaxel or Cisplatin + vinorelbine, participants who received only one of the two chemotherapies planned followed by Bevacizumab of each 21-day cycle up to 4 cycles.
Progression-free Survival (PFS)	3.7 months Interval 2.86 to 4.04	4.8 months Interval 4.14 to 5.52	—	—	—

SECONDARY outcome

Timeframe: Approximately 3 years

Population: Safety-evaluable enrolled participants: All participants who enrolled and received at least one dose of chemotherapy or Bevacizumab. N= Number of participants analyzed.

Treatment-emergent adverse events were events between administration of study drug and up to 30 days after last dose of study drug that were absent before treatment or that worsened relative to pre-treatment state.. Number of participants who had Grade \>=3TEAEs of pulmonary hemorrhage, gastrointestinal (GI) perforation, arterial thromboembolic (ATE) events, proteinuria, congestive heart failure (CHF), and hypertension were presented. Data presented up to data cutoff 18 July 2008.

Outcome measures

Outcome measures
Measure	Bevacizumab + Placebo n=524 Participants Participants who completed four cycles of chemotherapy + bevacizumab received Bevacizumab 15 milligram per kilogram (mg/kg) intravenously (IV) on Day 1 of every 21-day cycle along with matched Placebo to Erlotinib orally daily.	Bevacizumab + Erlotinib n=326 Participants Participants who completed four cycles of chemotherapy + bevacizumab received received IV dose of Bevacizumab 15 mg/kg on Day 1 of every 21-day cycle along with Erlotinib as 150 mg per day orally daily.	Carboplatin + Docetaxel n=162 Participants Participants received IV dose of Carboplatin at a dose based on the AUC of of 6 mg/mL × min and Docetaxel 75 mg/m\^2, respectively followed by Bevacizumab on Day 1 of each 21-day cycle up to 4 cycles.	Cisplatin + Gemcitabine n=104 Participants Participants received IV dose of Cisplatin 80 mg/m\^2 on Day 1 of each 21-day cycle and Gemcitabine 1000-1250 mg/m\^2 on Day 1 and Day 8 followed by Bevacizumab of each 21-day cycle up to 4 cycles.	Other n=28 Participants Included participants who received Cisplatin + Docetaxel or Cisplatin + vinorelbine, participants who received only one of the two chemotherapies planned followed by Bevacizumab of each 21-day cycle up to 4 cycles.
Number of Participants With Prospectively Identified Treatment Emergent Adverse Events (TEAE) During Chemotherapy Phase Pulmonary hemorrhage	6 participants	2 participants	3 participants	1 participants	2 participants
Number of Participants With Prospectively Identified Treatment Emergent Adverse Events (TEAE) During Chemotherapy Phase GI perforation	6 participants	0 participants	2 participants	0 participants	0 participants
Number of Participants With Prospectively Identified Treatment Emergent Adverse Events (TEAE) During Chemotherapy Phase ATE events	8 participants	6 participants	2 participants	1 participants	0 participants
Number of Participants With Prospectively Identified Treatment Emergent Adverse Events (TEAE) During Chemotherapy Phase Proteinuria	1 participants	5 participants	2 participants	2 participants	0 participants
Number of Participants With Prospectively Identified Treatment Emergent Adverse Events (TEAE) During Chemotherapy Phase CHF	3 participants	1 participants	1 participants	0 participants	0 participants

SECONDARY outcome

Timeframe: Approximately 3 years

Treatment-related adverse events are defined as new events that occur following subject entry into the study or events that worsen following study entry state and are judged by the investigator to be possibly, probably or definitely related to study medication. Pulmonary hemorrhage, GI perforation, ATE events, proteinuria, CHF, and hypertension were prospectively identified TEAEs of grade \>=3. Data presented until cut-off date 28 January 2009.

Outcome measures

Outcome measures
Measure	Bevacizumab + Placebo n=367 Participants Participants who completed four cycles of chemotherapy + bevacizumab received Bevacizumab 15 milligram per kilogram (mg/kg) intravenously (IV) on Day 1 of every 21-day cycle along with matched Placebo to Erlotinib orally daily.	Bevacizumab + Erlotinib n=368 Participants Participants who completed four cycles of chemotherapy + bevacizumab received received IV dose of Bevacizumab 15 mg/kg on Day 1 of every 21-day cycle along with Erlotinib as 150 mg per day orally daily.	Carboplatin + Docetaxel Participants received IV dose of Carboplatin at a dose based on the AUC of of 6 mg/mL × min and Docetaxel 75 mg/m\^2, respectively followed by Bevacizumab on Day 1 of each 21-day cycle up to 4 cycles.	Cisplatin + Gemcitabine Participants received IV dose of Cisplatin 80 mg/m\^2 on Day 1 of each 21-day cycle and Gemcitabine 1000-1250 mg/m\^2 on Day 1 and Day 8 followed by Bevacizumab of each 21-day cycle up to 4 cycles.	Other Included participants who received Cisplatin + Docetaxel or Cisplatin + vinorelbine, participants who received only one of the two chemotherapies planned followed by Bevacizumab of each 21-day cycle up to 4 cycles.
Number of Participants With Prospectively Identified Treatment Emergent Adverse Events (TEAE) During Post-Chemotherapy Phase Pulmonary hemorrhage	2 participants	3 participants	—	—	—
Number of Participants With Prospectively Identified Treatment Emergent Adverse Events (TEAE) During Post-Chemotherapy Phase GI perforation	0 participants	1 participants	—	—	—
Number of Participants With Prospectively Identified Treatment Emergent Adverse Events (TEAE) During Post-Chemotherapy Phase Proteinuria	7 participants	7 participants	—	—	—
Number of Participants With Prospectively Identified Treatment Emergent Adverse Events (TEAE) During Post-Chemotherapy Phase ATE events	5 participants	8 participants	—	—	—
Number of Participants With Prospectively Identified Treatment Emergent Adverse Events (TEAE) During Post-Chemotherapy Phase CHF	1 participants	3 participants	—	—	—
Number of Participants With Prospectively Identified Treatment Emergent Adverse Events (TEAE) During Post-Chemotherapy Phase Hypertension	22 participants	23 participants	—	—	—

SECONDARY outcome

Timeframe: Approximately 3.5 years

Population: Safety-evaluable randomized Participants: All randomized Participants who received at least one complete or partial dose of Bevacizumab + Erlotinib or Bevacizumab + Placebo. N= Number of participants analyzed. At the time of the 28 January 2009 data cutoff, an additional 25 patients had been randomized.

An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is a significant medical event. Data presented up to data cutoff 19 June 2009.

Outcome measures

Outcome measures
Measure	Bevacizumab + Placebo n=367 Participants Participants who completed four cycles of chemotherapy + bevacizumab received Bevacizumab 15 milligram per kilogram (mg/kg) intravenously (IV) on Day 1 of every 21-day cycle along with matched Placebo to Erlotinib orally daily.	Bevacizumab + Erlotinib n=368 Participants Participants who completed four cycles of chemotherapy + bevacizumab received received IV dose of Bevacizumab 15 mg/kg on Day 1 of every 21-day cycle along with Erlotinib as 150 mg per day orally daily.	Carboplatin + Docetaxel Participants received IV dose of Carboplatin at a dose based on the AUC of of 6 mg/mL × min and Docetaxel 75 mg/m\^2, respectively followed by Bevacizumab on Day 1 of each 21-day cycle up to 4 cycles.	Cisplatin + Gemcitabine Participants received IV dose of Cisplatin 80 mg/m\^2 on Day 1 of each 21-day cycle and Gemcitabine 1000-1250 mg/m\^2 on Day 1 and Day 8 followed by Bevacizumab of each 21-day cycle up to 4 cycles.	Other Included participants who received Cisplatin + Docetaxel or Cisplatin + vinorelbine, participants who received only one of the two chemotherapies planned followed by Bevacizumab of each 21-day cycle up to 4 cycles.
Number of Participants With Any Adverse Events During Post-Chemotherapy Phase	319 participants	353 participants	—	—	—

SECONDARY outcome

Timeframe: Approximately 3 years

Population: Enrolled participants: All participants who were enrolled in the study. N= Number of participants analyzed.

Participants who experienced disease progression were discontinued from the study. Data presented up to data cutoff (18 July 2008).

Outcome measures

Outcome measures
Measure	Bevacizumab + Placebo n=524 Participants Participants who completed four cycles of chemotherapy + bevacizumab received Bevacizumab 15 milligram per kilogram (mg/kg) intravenously (IV) on Day 1 of every 21-day cycle along with matched Placebo to Erlotinib orally daily.	Bevacizumab + Erlotinib n=326 Participants Participants who completed four cycles of chemotherapy + bevacizumab received received IV dose of Bevacizumab 15 mg/kg on Day 1 of every 21-day cycle along with Erlotinib as 150 mg per day orally daily.	Carboplatin + Docetaxel n=162 Participants Participants received IV dose of Carboplatin at a dose based on the AUC of of 6 mg/mL × min and Docetaxel 75 mg/m\^2, respectively followed by Bevacizumab on Day 1 of each 21-day cycle up to 4 cycles.	Cisplatin + Gemcitabine n=104 Participants Participants received IV dose of Cisplatin 80 mg/m\^2 on Day 1 of each 21-day cycle and Gemcitabine 1000-1250 mg/m\^2 on Day 1 and Day 8 followed by Bevacizumab of each 21-day cycle up to 4 cycles.	Other n=29 Participants Included participants who received Cisplatin + Docetaxel or Cisplatin + vinorelbine, participants who received only one of the two chemotherapies planned followed by Bevacizumab of each 21-day cycle up to 4 cycles.
Incidence of Study Treatment Discontinuation for Reasons Other Than Disease Progression in Chemotherapy Phase Adverse Event	54 participants	40 participants	22 participants	14 participants	8 participants
Incidence of Study Treatment Discontinuation for Reasons Other Than Disease Progression in Chemotherapy Phase Concomitant/ancillary therapy	13 participants	6 participants	5 participants	1 participants	2 participants
Incidence of Study Treatment Discontinuation for Reasons Other Than Disease Progression in Chemotherapy Phase Patient's Decision to Discontinue	16 participants	6 participants	8 participants	5 participants	0 participants
Incidence of Study Treatment Discontinuation for Reasons Other Than Disease Progression in Chemotherapy Phase Investigator's Decision	13 participants	5 participants	7 participants	3 participants	0 participants
Incidence of Study Treatment Discontinuation for Reasons Other Than Disease Progression in Chemotherapy Phase Unwillingness or inability to comply with study	4 participants	0 participants	0 participants	1 participants	1 participants
Incidence of Study Treatment Discontinuation for Reasons Other Than Disease Progression in Chemotherapy Phase Unrelated intercurrent illness	1 participants	0 participants	1 participants	1 participants	0 participants

SECONDARY outcome

Timeframe: Approximately 3 years

Population: Intent to treat (ITT) population included all participants who were randomized during the post-chemotherapy phase.. N= Number of participants analyzed.

Participants in post-chemotherapy phase were discontinued from the study for the reasons other than disease progression. Data presented Up to data cutoff 18 July 2008.

Outcome measures

Outcome measures
Measure	Bevacizumab + Placebo n=373 Participants Participants who completed four cycles of chemotherapy + bevacizumab received Bevacizumab 15 milligram per kilogram (mg/kg) intravenously (IV) on Day 1 of every 21-day cycle along with matched Placebo to Erlotinib orally daily.	Bevacizumab + Erlotinib n=370 Participants Participants who completed four cycles of chemotherapy + bevacizumab received received IV dose of Bevacizumab 15 mg/kg on Day 1 of every 21-day cycle along with Erlotinib as 150 mg per day orally daily.	Carboplatin + Docetaxel Participants received IV dose of Carboplatin at a dose based on the AUC of of 6 mg/mL × min and Docetaxel 75 mg/m\^2, respectively followed by Bevacizumab on Day 1 of each 21-day cycle up to 4 cycles.	Cisplatin + Gemcitabine Participants received IV dose of Cisplatin 80 mg/m\^2 on Day 1 of each 21-day cycle and Gemcitabine 1000-1250 mg/m\^2 on Day 1 and Day 8 followed by Bevacizumab of each 21-day cycle up to 4 cycles.	Other Included participants who received Cisplatin + Docetaxel or Cisplatin + vinorelbine, participants who received only one of the two chemotherapies planned followed by Bevacizumab of each 21-day cycle up to 4 cycles.
Incidence of Study Treatment Discontinuation Erlotinib/placebo: Sponsor's decision	1 participants	0 participants	—	—	—
Incidence of Study Treatment Discontinuation Bevacizumab: AE	34 participants	38 participants	—	—	—
Incidence of Study Treatment Discontinuation Bevacizumab: Concomitant/ancillary therapy	5 participants	5 participants	—	—	—
Incidence of Study Treatment Discontinuation Bevacizumab: Patient's Decision to Discontinue	4 participants	8 participants	—	—	—
Incidence of Study Treatment Discontinuation Bevacizumab: Investigator's Decision	8 participants	11 participants	—	—	—
Incidence of Study Treatment Discontinuation Bevacizumab: Unwillingness or inability to comply	4 participants	5 participants	—	—	—
Incidence of Study Treatment Discontinuation Bevacizumab: Unrelated intercurrent illness	0 participants	1 participants	—	—	—
Incidence of Study Treatment Discontinuation Bevacizumab: Sponsor's decision	1 participants	0 participants	—	—	—
Incidence of Study Treatment Discontinuation Bevacizumab: Lost to follow-up	0 participants	1 participants	—	—	—
Incidence of Study Treatment Discontinuation Erlotinib/placebo: AE	22 participants	48 participants	—	—	—
Incidence of Study Treatment Discontinuation Erlotinib/placebo: Concomitant/ancillary therapy	4 participants	7 participants	—	—	—
Incidence of Study Treatment Discontinuation Erlotinib/placebo:Patient's Decision	5 participants	10 participants	—	—	—
Incidence of Study Treatment Discontinuation Erlotinib/placebo: Investigator's Decision	6 participants	12 participants	—	—	—
Incidence of Study Treatment Discontinuation Erlotinib/placebo:Unwillingness/inability comply	4 participants	2 participants	—	—	—
Incidence of Study Treatment Discontinuation Erlotinib/placebo: Unrelated intercurrent illness	0 participants	2 participants	—	—	—
Incidence of Study Treatment Discontinuation Erlotinib/placebo: Lost to follow-up	0 participants	1 participants	—	—	—

SECONDARY outcome

Timeframe: Approximately 3.5 years

Population: Intent-to-treat population included all participants who were randomized during the post-chemotherapy phase.

Overall survival was defined as the length of time from randomization to death.

Outcome measures

Outcome measures
Measure	Bevacizumab + Placebo n=373 Participants Participants who completed four cycles of chemotherapy + bevacizumab received Bevacizumab 15 milligram per kilogram (mg/kg) intravenously (IV) on Day 1 of every 21-day cycle along with matched Placebo to Erlotinib orally daily.	Bevacizumab + Erlotinib n=370 Participants Participants who completed four cycles of chemotherapy + bevacizumab received received IV dose of Bevacizumab 15 mg/kg on Day 1 of every 21-day cycle along with Erlotinib as 150 mg per day orally daily.	Carboplatin + Docetaxel Participants received IV dose of Carboplatin at a dose based on the AUC of of 6 mg/mL × min and Docetaxel 75 mg/m\^2, respectively followed by Bevacizumab on Day 1 of each 21-day cycle up to 4 cycles.	Cisplatin + Gemcitabine Participants received IV dose of Cisplatin 80 mg/m\^2 on Day 1 of each 21-day cycle and Gemcitabine 1000-1250 mg/m\^2 on Day 1 and Day 8 followed by Bevacizumab of each 21-day cycle up to 4 cycles.	Other Included participants who received Cisplatin + Docetaxel or Cisplatin + vinorelbine, participants who received only one of the two chemotherapies planned followed by Bevacizumab of each 21-day cycle up to 4 cycles.
Overall Survival	13.3 months Interval 12.12 to 14.52	14.4 months Interval 12.29 to 18.6	—	—	—

Adverse Events

Bevacizumab + Placebo

Serious events: 63 serious events

Other events: 288 other events

Deaths: 0 deaths

Bevacizumab + Erlotinib

Serious events: 86 serious events

Other events: 341 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Roche Trial Information Hotline

F. Hoffmann-La Roche AG

Phone: +41 616878333

Email: [email protected]

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

Measure	Bevacizumab + Placebo n=367 participants at risk Participants who completed four cycles of chemotherapy + bevacizumab received Bevacizumab 15 milligram per kilogram (mg/kg) intravenously (IV) on Day 1 of every 21-day cycle along with matched Placebo to Erlotinib orally daily.	Bevacizumab + Erlotinib n=368 participants at risk Participants who completed four cycles of chemotherapy + bevacizumab received received IV dose of Bevacizumab 15 mg/kg on Day 1 of every 21-day cycle along with Erlotinib as 150 mg per day orally daily.
Blood and lymphatic system disorders Anaemia	5.7% 21/367 • Up to 30 days after discontinuation of study treatment Safety-evaluable randomized participants who had received at least one complete or partial dose of bevacizumab or erlotinib/placebo.	5.2% 19/368 • Up to 30 days after discontinuation of study treatment Safety-evaluable randomized participants who had received at least one complete or partial dose of bevacizumab or erlotinib/placebo.
Gastrointestinal disorders Abdominal pain	3.3% 12/367 • Up to 30 days after discontinuation of study treatment Safety-evaluable randomized participants who had received at least one complete or partial dose of bevacizumab or erlotinib/placebo.	5.2% 19/368 • Up to 30 days after discontinuation of study treatment Safety-evaluable randomized participants who had received at least one complete or partial dose of bevacizumab or erlotinib/placebo.
Gastrointestinal disorders Constipation	9.0% 33/367 • Up to 30 days after discontinuation of study treatment Safety-evaluable randomized participants who had received at least one complete or partial dose of bevacizumab or erlotinib/placebo.	9.2% 34/368 • Up to 30 days after discontinuation of study treatment Safety-evaluable randomized participants who had received at least one complete or partial dose of bevacizumab or erlotinib/placebo.
Gastrointestinal disorders Diarrhoea	19.6% 72/367 • Up to 30 days after discontinuation of study treatment Safety-evaluable randomized participants who had received at least one complete or partial dose of bevacizumab or erlotinib/placebo.	51.1% 188/368 • Up to 30 days after discontinuation of study treatment Safety-evaluable randomized participants who had received at least one complete or partial dose of bevacizumab or erlotinib/placebo.
Gastrointestinal disorders Nausea	10.6% 39/367 • Up to 30 days after discontinuation of study treatment Safety-evaluable randomized participants who had received at least one complete or partial dose of bevacizumab or erlotinib/placebo.	20.4% 75/368 • Up to 30 days after discontinuation of study treatment Safety-evaluable randomized participants who had received at least one complete or partial dose of bevacizumab or erlotinib/placebo.
Gastrointestinal disorders Stomatitis	2.5% 9/367 • Up to 30 days after discontinuation of study treatment Safety-evaluable randomized participants who had received at least one complete or partial dose of bevacizumab or erlotinib/placebo.	7.3% 27/368 • Up to 30 days after discontinuation of study treatment Safety-evaluable randomized participants who had received at least one complete or partial dose of bevacizumab or erlotinib/placebo.
Gastrointestinal disorders Vomiting	7.1% 26/367 • Up to 30 days after discontinuation of study treatment Safety-evaluable randomized participants who had received at least one complete or partial dose of bevacizumab or erlotinib/placebo.	10.3% 38/368 • Up to 30 days after discontinuation of study treatment Safety-evaluable randomized participants who had received at least one complete or partial dose of bevacizumab or erlotinib/placebo.
General disorders Asthenia	3.3% 12/367 • Up to 30 days after discontinuation of study treatment Safety-evaluable randomized participants who had received at least one complete or partial dose of bevacizumab or erlotinib/placebo.	5.4% 20/368 • Up to 30 days after discontinuation of study treatment Safety-evaluable randomized participants who had received at least one complete or partial dose of bevacizumab or erlotinib/placebo.
General disorders Chest pain	6.5% 24/367 • Up to 30 days after discontinuation of study treatment Safety-evaluable randomized participants who had received at least one complete or partial dose of bevacizumab or erlotinib/placebo.	4.9% 18/368 • Up to 30 days after discontinuation of study treatment Safety-evaluable randomized participants who had received at least one complete or partial dose of bevacizumab or erlotinib/placebo.
General disorders Fatigue	24.8% 91/367 • Up to 30 days after discontinuation of study treatment Safety-evaluable randomized participants who had received at least one complete or partial dose of bevacizumab or erlotinib/placebo.	34.2% 126/368 • Up to 30 days after discontinuation of study treatment Safety-evaluable randomized participants who had received at least one complete or partial dose of bevacizumab or erlotinib/placebo.
General disorders Mucosal inflammation	0.82% 3/367 • Up to 30 days after discontinuation of study treatment Safety-evaluable randomized participants who had received at least one complete or partial dose of bevacizumab or erlotinib/placebo.	7.1% 26/368 • Up to 30 days after discontinuation of study treatment Safety-evaluable randomized participants who had received at least one complete or partial dose of bevacizumab or erlotinib/placebo.
General disorders Pyrexia	2.5% 9/367 • Up to 30 days after discontinuation of study treatment Safety-evaluable randomized participants who had received at least one complete or partial dose of bevacizumab or erlotinib/placebo.	5.4% 20/368 • Up to 30 days after discontinuation of study treatment Safety-evaluable randomized participants who had received at least one complete or partial dose of bevacizumab or erlotinib/placebo.
Infections and infestations Urinary tract infection	2.5% 9/367 • Up to 30 days after discontinuation of study treatment Safety-evaluable randomized participants who had received at least one complete or partial dose of bevacizumab or erlotinib/placebo.	6.2% 23/368 • Up to 30 days after discontinuation of study treatment Safety-evaluable randomized participants who had received at least one complete or partial dose of bevacizumab or erlotinib/placebo.
Investigations Weight decreased	5.7% 21/367 • Up to 30 days after discontinuation of study treatment Safety-evaluable randomized participants who had received at least one complete or partial dose of bevacizumab or erlotinib/placebo.	11.7% 43/368 • Up to 30 days after discontinuation of study treatment Safety-evaluable randomized participants who had received at least one complete or partial dose of bevacizumab or erlotinib/placebo.
Metabolism and nutrition disorders Anorexia	9.8% 36/367 • Up to 30 days after discontinuation of study treatment Safety-evaluable randomized participants who had received at least one complete or partial dose of bevacizumab or erlotinib/placebo.	20.7% 76/368 • Up to 30 days after discontinuation of study treatment Safety-evaluable randomized participants who had received at least one complete or partial dose of bevacizumab or erlotinib/placebo.
Musculoskeletal and connective tissue disorders Arthralgia	11.4% 42/367 • Up to 30 days after discontinuation of study treatment Safety-evaluable randomized participants who had received at least one complete or partial dose of bevacizumab or erlotinib/placebo.	5.4% 20/368 • Up to 30 days after discontinuation of study treatment Safety-evaluable randomized participants who had received at least one complete or partial dose of bevacizumab or erlotinib/placebo.
Musculoskeletal and connective tissue disorders Back pain	9.3% 34/367 • Up to 30 days after discontinuation of study treatment Safety-evaluable randomized participants who had received at least one complete or partial dose of bevacizumab or erlotinib/placebo.	10.6% 39/368 • Up to 30 days after discontinuation of study treatment Safety-evaluable randomized participants who had received at least one complete or partial dose of bevacizumab or erlotinib/placebo.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	9.5% 35/367 • Up to 30 days after discontinuation of study treatment Safety-evaluable randomized participants who had received at least one complete or partial dose of bevacizumab or erlotinib/placebo.	7.6% 28/368 • Up to 30 days after discontinuation of study treatment Safety-evaluable randomized participants who had received at least one complete or partial dose of bevacizumab or erlotinib/placebo.
Musculoskeletal and connective tissue disorders Pain in extremity	6.3% 23/367 • Up to 30 days after discontinuation of study treatment Safety-evaluable randomized participants who had received at least one complete or partial dose of bevacizumab or erlotinib/placebo.	7.9% 29/368 • Up to 30 days after discontinuation of study treatment Safety-evaluable randomized participants who had received at least one complete or partial dose of bevacizumab or erlotinib/placebo.
Nervous system disorders Dizziness	4.9% 18/367 • Up to 30 days after discontinuation of study treatment Safety-evaluable randomized participants who had received at least one complete or partial dose of bevacizumab or erlotinib/placebo.	6.2% 23/368 • Up to 30 days after discontinuation of study treatment Safety-evaluable randomized participants who had received at least one complete or partial dose of bevacizumab or erlotinib/placebo.
Nervous system disorders Dysgeusia	2.7% 10/367 • Up to 30 days after discontinuation of study treatment Safety-evaluable randomized participants who had received at least one complete or partial dose of bevacizumab or erlotinib/placebo.	6.2% 23/368 • Up to 30 days after discontinuation of study treatment Safety-evaluable randomized participants who had received at least one complete or partial dose of bevacizumab or erlotinib/placebo.
Nervous system disorders Headache	12.3% 45/367 • Up to 30 days after discontinuation of study treatment Safety-evaluable randomized participants who had received at least one complete or partial dose of bevacizumab or erlotinib/placebo.	10.3% 38/368 • Up to 30 days after discontinuation of study treatment Safety-evaluable randomized participants who had received at least one complete or partial dose of bevacizumab or erlotinib/placebo.
Nervous system disorders Neuropathy peripheral	6.8% 25/367 • Up to 30 days after discontinuation of study treatment Safety-evaluable randomized participants who had received at least one complete or partial dose of bevacizumab or erlotinib/placebo.	7.6% 28/368 • Up to 30 days after discontinuation of study treatment Safety-evaluable randomized participants who had received at least one complete or partial dose of bevacizumab or erlotinib/placebo.
Psychiatric disorders Depression	2.7% 10/367 • Up to 30 days after discontinuation of study treatment Safety-evaluable randomized participants who had received at least one complete or partial dose of bevacizumab or erlotinib/placebo.	8.7% 32/368 • Up to 30 days after discontinuation of study treatment Safety-evaluable randomized participants who had received at least one complete or partial dose of bevacizumab or erlotinib/placebo.
Psychiatric disorders Insomnia	3.5% 13/367 • Up to 30 days after discontinuation of study treatment Safety-evaluable randomized participants who had received at least one complete or partial dose of bevacizumab or erlotinib/placebo.	6.2% 23/368 • Up to 30 days after discontinuation of study treatment Safety-evaluable randomized participants who had received at least one complete or partial dose of bevacizumab or erlotinib/placebo.
Renal and urinary disorders Proteinuria	5.7% 21/367 • Up to 30 days after discontinuation of study treatment Safety-evaluable randomized participants who had received at least one complete or partial dose of bevacizumab or erlotinib/placebo.	6.5% 24/368 • Up to 30 days after discontinuation of study treatment Safety-evaluable randomized participants who had received at least one complete or partial dose of bevacizumab or erlotinib/placebo.
Respiratory, thoracic and mediastinal disorders Cough	18.0% 66/367 • Up to 30 days after discontinuation of study treatment Safety-evaluable randomized participants who had received at least one complete or partial dose of bevacizumab or erlotinib/placebo.	17.1% 63/368 • Up to 30 days after discontinuation of study treatment Safety-evaluable randomized participants who had received at least one complete or partial dose of bevacizumab or erlotinib/placebo.
Respiratory, thoracic and mediastinal disorders Dysphonia	5.7% 21/367 • Up to 30 days after discontinuation of study treatment Safety-evaluable randomized participants who had received at least one complete or partial dose of bevacizumab or erlotinib/placebo.	4.1% 15/368 • Up to 30 days after discontinuation of study treatment Safety-evaluable randomized participants who had received at least one complete or partial dose of bevacizumab or erlotinib/placebo.
Respiratory, thoracic and mediastinal disorders Dyspnoea	12.0% 44/367 • Up to 30 days after discontinuation of study treatment Safety-evaluable randomized participants who had received at least one complete or partial dose of bevacizumab or erlotinib/placebo.	11.4% 42/368 • Up to 30 days after discontinuation of study treatment Safety-evaluable randomized participants who had received at least one complete or partial dose of bevacizumab or erlotinib/placebo.
Respiratory, thoracic and mediastinal disorders Epistaxis	8.7% 32/367 • Up to 30 days after discontinuation of study treatment Safety-evaluable randomized participants who had received at least one complete or partial dose of bevacizumab or erlotinib/placebo.	10.9% 40/368 • Up to 30 days after discontinuation of study treatment Safety-evaluable randomized participants who had received at least one complete or partial dose of bevacizumab or erlotinib/placebo.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	2.7% 10/367 • Up to 30 days after discontinuation of study treatment Safety-evaluable randomized participants who had received at least one complete or partial dose of bevacizumab or erlotinib/placebo.	5.2% 19/368 • Up to 30 days after discontinuation of study treatment Safety-evaluable randomized participants who had received at least one complete or partial dose of bevacizumab or erlotinib/placebo.
Skin and subcutaneous tissue disorders Alopecia	4.9% 18/367 • Up to 30 days after discontinuation of study treatment Safety-evaluable randomized participants who had received at least one complete or partial dose of bevacizumab or erlotinib/placebo.	7.1% 26/368 • Up to 30 days after discontinuation of study treatment Safety-evaluable randomized participants who had received at least one complete or partial dose of bevacizumab or erlotinib/placebo.
Skin and subcutaneous tissue disorders Dermatitis acneiform	4.1% 15/367 • Up to 30 days after discontinuation of study treatment Safety-evaluable randomized participants who had received at least one complete or partial dose of bevacizumab or erlotinib/placebo.	15.8% 58/368 • Up to 30 days after discontinuation of study treatment Safety-evaluable randomized participants who had received at least one complete or partial dose of bevacizumab or erlotinib/placebo.
Skin and subcutaneous tissue disorders Dry skin	6.3% 23/367 • Up to 30 days after discontinuation of study treatment Safety-evaluable randomized participants who had received at least one complete or partial dose of bevacizumab or erlotinib/placebo.	12.0% 44/368 • Up to 30 days after discontinuation of study treatment Safety-evaluable randomized participants who had received at least one complete or partial dose of bevacizumab or erlotinib/placebo.
Skin and subcutaneous tissue disorders Pruritus	6.8% 25/367 • Up to 30 days after discontinuation of study treatment Safety-evaluable randomized participants who had received at least one complete or partial dose of bevacizumab or erlotinib/placebo.	5.7% 21/368 • Up to 30 days after discontinuation of study treatment Safety-evaluable randomized participants who had received at least one complete or partial dose of bevacizumab or erlotinib/placebo.
Skin and subcutaneous tissue disorders Rash	18.8% 69/367 • Up to 30 days after discontinuation of study treatment Safety-evaluable randomized participants who had received at least one complete or partial dose of bevacizumab or erlotinib/placebo.	55.4% 204/368 • Up to 30 days after discontinuation of study treatment Safety-evaluable randomized participants who had received at least one complete or partial dose of bevacizumab or erlotinib/placebo.
Vascular disorders Hypertension	23.2% 85/367 • Up to 30 days after discontinuation of study treatment Safety-evaluable randomized participants who had received at least one complete or partial dose of bevacizumab or erlotinib/placebo.	23.6% 87/368 • Up to 30 days after discontinuation of study treatment Safety-evaluable randomized participants who had received at least one complete or partial dose of bevacizumab or erlotinib/placebo.