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

• ClinicalTrials.gov Identifier: NCT00257608
• Recruitment Status: Completed
• First Posted: November 23, 2005
• Results First Posted: March 15, 2016
• Last Update Posted: April 18, 2016
• Sponsor: Genentech, Inc.
• Information provided by (Responsible Party): Genentech, Inc.

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Non-Small Cell Lung Cancer
• Interventions: Drug: bevacizumab; Drug: placebo; Drug: erlotinib HCl
• Enrollment: 1145

Participant Flow

Recruitment Details	This study was conducted in 14 countries between 10 January 2006 and 19 June 2009.
Pre-assignment Details

Arm/Group Title	Bevacizumab + Chemotherapy	Bevacizumab + Placebo	Bevacizumab + Erlotinib
Arm/Group Description	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.	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.	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.
Period Title: Chemotherapy Phase
Started	1145	0	0
Completed	769	0	0
Not Completed	376	0	0
Reason Not Completed
Adverse Event	138	0	0
Disease progression	139	0	0
Unwillingness or inability to comply	6	0	0
Need for concomitant/ancillary therapy	27	0	0
Patient's decision to discontinue	35	0	0
Unrelated intercurrent illness	3	0	0
Physician Decision	28	0	0
Period Title: Post Chemotherapy Phase
Started	0	373	370
Completed	0	109	126
Not Completed	0	264	244
Reason Not Completed
Adverse Event	0	34	38
Disease progression	0	204	168
Unwillingness or inability to comply	0	4	5
Need for concomitant/ancillary therapy	0	5	5
Patient's decision to discontinue	0	4	8
Unrelated intercurrent illness	0	0	1
Lost to Follow-up	0	0	1
Physician Decision	0	8	11
Sponsor's decision to terminate study	0	1	0
Not treated	0	4	7

Baseline Characteristics

Arm/Group Title		Bevacizumab + Placebo	Bevacizumab + Erlotinib	Total
Arm/Group Description		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	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 of all reporting groups
Overall Number of Baseline Participants		373	370	743
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	373 participants	370 participants	743 participants
		62.8 (10.8)	62.9 (10.3)	62.9 (10.6)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	373 participants	370 participants	743 participants
	Female	177 47.5%	177 47.8%	354 47.6%
	Male	196 52.5%	193 52.2%	389 52.4%

Outcome Measures

1. Primary Outcome

Title	Progression-free Survival (PFS)
Description	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.
Time Frame	Approximately 3 years

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Bevacizumab + Placebo	Bevacizumab + Erlotinib
Arm/Group Description:	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.	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.
Overall Number of Participants Analyzed	373	370
Median (95% Confidence Interval); Unit of Measure: months
	3.7; (2.86 to 4.04)	4.8; (4.14 to 5.52)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bevacizumab + Placebo, Bevacizumab + Erlotinib
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0006
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio, log
	Estimated Value	0.708
	Confidence Interval	(2-Sided) 95%; 0.580 to 0.864
	Estimation Comments	[Not Specified]

2. Secondary Outcome

Title	Number of Participants With Prospectively Identified Treatment Emergent Adverse Events (TEAE) During Chemotherapy Phase
Description	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.
Time Frame	Approximately 3 years

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Carboplatin + Paclitaxel	Carboplatin + Gemcitabine	Carboplatin + Docetaxel	Cisplatin + Gemcitabine	Other
Arm/Group Description:	Participants received Intravenous (IV) dose of Carboplatin at a dose based on an area under the concentration-time curve (AUC) of 6 milligram /milliliter (mg/mL) × minute (min) and Paclitaxel 200 milligram per square meter (mg/m^2) over 3 hours, respectively followed by Bevacizumab on Day 1 of each 21-day cycle up to 4 cycles.	Participants received IV dose of Carboplatin at a dose based on the AUC of 5 mg/mL × min on Day 1 of each 21-day cycle and Gemcitabine 1200 mg/m^2 on Day 1 and Day 8 followed by Bevacizumab of each 21-day cycle up to 4 cycles.	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.	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.	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 Number of Participants Analyzed	524	326	162	104	28
Measure Type: Number; Unit of Measure: participants
Pulmonary hemorrhage	6	2	3	1	2
GI perforation	6	0	2	0	0
ATE events	8	6	2	1	0
Proteinuria	1	5	2	2	0
CHF	3	1	1	0	0

3. Secondary Outcome

Title	Number of Participants With Prospectively Identified Treatment Emergent Adverse Events (TEAE) During Post-Chemotherapy Phase
Description	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.
Time Frame	Approximately 3 years

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Bevacizumab + Placebo	Bevacizumab + Erlotinib
Arm/Group Description:	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.	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.
Overall Number of Participants Analyzed	367	368
Measure Type: Number; Unit of Measure: participants
Pulmonary hemorrhage	2	3
GI perforation	0	1
ATE events	5	8
Proteinuria	7	7
CHF	1	3
Hypertension	22	23

4. Secondary Outcome

Title	Number of Participants With Any Adverse Events During Post-Chemotherapy Phase
Description	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.
Time Frame	Approximately 3.5 years

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Bevacizumab + Placebo	Bevacizumab + Erlotinib
Arm/Group Description:	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.	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.
Overall Number of Participants Analyzed	367	368
Measure Type: Number; Unit of Measure: participants
	319	353

5. Secondary Outcome

Title	Incidence of Study Treatment Discontinuation for Reasons Other Than Disease Progression in Chemotherapy Phase
Description	Participants who experienced disease progression were discontinued from the study. Data presented up to data cutoff (18 July 2008).
Time Frame	Approximately 3 years

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Carboplatin + Paclitaxel	Carboplatin + Gemcitabine	Carboplatin + Docetaxel	Cisplatin + Gemcitabine	Other
Arm/Group Description:	Participants received Intravenous (IV) dose of Carboplatin at a dose based on an area under the concentration time curve (AUC) of 6 milligram /milliliter (mg/mL) × minute (min) and Paclitaxel 200 milligram per square meter (mg/m^2) over 3 hours, respectively followed by Bevacizumab on Day 1 of each 21-day cycle up to 4 cycles.	Participants received IV dose of Carboplatin at a dose based on the AUC of 5 mg/mL × min on Day 1 of each 21-day cycle and Gemcitabine 1200 mg/m^2 on Day 1 and Day 8 followed by Bevacizumab of each 21-day cycle up to 4 cycles.	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.	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.	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 Number of Participants Analyzed	524	326	162	104	29
Measure Type: Number; Unit of Measure: participants
Adverse Event	54	40	22	14	8
Concomitant/ancillary therapy	13	6	5	1	2
Patient's Decision to Discontinue	16	6	8	5	0
Investigator's Decision	13	5	7	3	0
Unwillingness or inability to comply with study	4	0	0	1	1
Unrelated intercurrent illness	1	0	1	1	0

6. Secondary Outcome

Title	Incidence of Study Treatment Discontinuation
Description	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.
Time Frame	Approximately 3 years

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Bevacizumab + Placebo	Bevacizumab + Erlotinib
Arm/Group Description:	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.	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.
Overall Number of Participants Analyzed	373	370
Measure Type: Number; Unit of Measure: participants
Bevacizumab: AE	34	38
Bevacizumab: Concomitant/ancillary therapy	5	5
Bevacizumab: Patient's Decision to Discontinue	4	8
Bevacizumab: Investigator's Decision	8	11
Bevacizumab: Unwillingness or inability to comply	4	5
Bevacizumab: Unrelated intercurrent illness	0	1
Bevacizumab: Sponsor's decision	1	0
Bevacizumab: Lost to follow-up	0	1
Erlotinib/placebo: AE	22	48
Erlotinib/placebo: Concomitant/ancillary therapy	4	7
Erlotinib/placebo:Patient's Decision	5	10
Erlotinib/placebo: Investigator's Decision	6	12
Erlotinib/placebo:Unwillingness/inability comply	4	2
Erlotinib/placebo: Unrelated intercurrent illness	0	2
Erlotinib/placebo: Sponsor's decision	1	0
Erlotinib/placebo: Lost to follow-up	0	1

7. Secondary Outcome

Title	Overall Survival
Description	Overall survival was defined as the length of time from randomization to death.
Time Frame	Approximately 3.5 years

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Bevacizumab + Placebo	Bevacizumab + Erlotinib
Arm/Group Description:	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.	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.
Overall Number of Participants Analyzed	373	370
Median (95% Confidence Interval); Unit of Measure: months
	13.3; (12.12 to 14.52)	14.4; (12.29 to 18.60)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bevacizumab + Placebo, Bevacizumab + Erlotinib
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.5341
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.917
	Confidence Interval	(2-Sided) 95%; 0.698 to 1.205
	Estimation Comments	[Not Specified]

Adverse Events

Time Frame	Up to 30 days after discontinuation of study treatment
Adverse Event Reporting Description	Safety-evaluable randomized participants who had received at least one complete or partial dose of bevacizumab or erlotinib/placebo.
Arm/Group Title	Bevacizumab + Placebo	Bevacizumab + Erlotinib
Arm/Group Description	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.	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.
All-Cause Mortality
	Bevacizumab + Placebo	Bevacizumab + Erlotinib
	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--
Serious Adverse Events
	Bevacizumab + Placebo	Bevacizumab + Erlotinib
	Affected / at Risk (%)	Affected / at Risk (%)
Total	63/367 (17.17%)	86/368 (23.37%)
Blood and lymphatic system disorders
Febrile neutropenia † 1	1/367 (0.27%)	0/368 (0.00%)
Haemolytic anaemia † 1	0/367 (0.00%)	1/368 (0.27%)
Neutropenia † 1	0/367 (0.00%)	1/368 (0.27%)
Cardiac disorders
Atrial fibrillation † 1	3/367 (0.82%)	0/368 (0.00%)
Cardiac failure congestive † 1	2/367 (0.54%)	1/368 (0.27%)
Cardiac arrest † 1	0/367 (0.00%)	2/368 (0.54%)
Pericardial effusion † 1	2/367 (0.54%)	0/368 (0.00%)
Acute myocardial infarction † 1	1/367 (0.27%)	0/368 (0.00%)
Atrial tachycardia † 1	0/367 (0.00%)	1/368 (0.27%)
Bradycardia † 1	0/367 (0.00%)	1/368 (0.27%)
Myocardial infarction † 1	1/367 (0.27%)	0/368 (0.00%)
Sinus arrhythmia † 1	0/367 (0.00%)	1/368 (0.27%)
Endocrine disorders
Adrenal insufficiency † 1	1/367 (0.27%)	1/368 (0.27%)
Gastrointestinal disorders
Diarrhoea † 1	2/367 (0.54%)	4/368 (1.09%)
Vomiting † 1	3/367 (0.82%)	2/368 (0.54%)
Gastrointestinal haemorrhage † 1	2/367 (0.54%)	1/368 (0.27%)
Nausea † 1	1/367 (0.27%)	2/368 (0.54%)
Small intestinal obstruction † 1	1/367 (0.27%)	1/368 (0.27%)
Abdominal pain † 1	1/367 (0.27%)	0/368 (0.00%)
Constipation † 1	0/367 (0.00%)	1/368 (0.27%)
Food poisoning † 1	0/367 (0.00%)	1/368 (0.27%)
Gastrointestinal inflammation † 1	0/367 (0.00%)	1/368 (0.27%)
Large intestine perforation † 1	0/367 (0.00%)	1/368 (0.27%)
Oesophageal fistula † 1	0/367 (0.00%)	1/368 (0.27%)
Oesophagitis † 1	0/367 (0.00%)	1/368 (0.27%)
Pancreatitis † 1	1/367 (0.27%)	0/368 (0.00%)
Pancreatitis acute † 1	0/367 (0.00%)	1/368 (0.27%)
General disorders
Chest pain † 1	2/367 (0.54%)	3/368 (0.82%)
Pyrexia † 1	0/367 (0.00%)	5/368 (1.36%)
Asthenia † 1	0/367 (0.00%)	2/368 (0.54%)
Death † 1	1/367 (0.27%)	1/368 (0.27%)
Pain † 1	1/367 (0.27%)	1/368 (0.27%)
Hyperthermia † 1	1/367 (0.27%)	0/368 (0.00%)
Mucosal inflammation † 1	0/367 (0.00%)	1/368 (0.27%)
Performance status decreased † 1	0/367 (0.00%)	1/368 (0.27%)
Hepatobiliary disorders
Cholecystitis † 1	0/367 (0.00%)	2/368 (0.54%)
Cholelithiasis † 1	0/367 (0.00%)	1/368 (0.27%)
Cholestasis † 1	0/367 (0.00%)	1/368 (0.27%)
Hepatitis acute † 1	1/367 (0.27%)	0/368 (0.00%)
Hyperbilirubinaemia † 1	1/367 (0.27%)	0/368 (0.00%)
Infections and infestations
Pneumonia † 1	4/367 (1.09%)	4/368 (1.09%)
Bronchitis † 1	1/367 (0.27%)	1/368 (0.27%)
Gastroenteritis † 1	0/367 (0.00%)	2/368 (0.54%)
Infection † 1	1/367 (0.27%)	1/368 (0.27%)
Lobar pneumonia † 1	2/367 (0.54%)	0/368 (0.00%)
Sepsis † 1	0/367 (0.00%)	2/368 (0.54%)
Catheter site infection † 1	1/367 (0.27%)	0/368 (0.00%)
Cellulitis † 1	1/367 (0.27%)	0/368 (0.00%)
Encephalitic infection † 1	1/367 (0.27%)	0/368 (0.00%)
Escherichia infection † 1	1/367 (0.27%)	0/368 (0.00%)
Incision site infection † 1	1/367 (0.27%)	0/368 (0.00%)
Influenza † 1	0/367 (0.00%)	1/368 (0.27%)
Lower respiratory tract infection † 1	1/367 (0.27%)	0/368 (0.00%)
Staphylococcal abscess † 1	0/367 (0.00%)	1/368 (0.27%)
Wound infection † 1	1/367 (0.27%)	0/368 (0.00%)
Injury, poisoning and procedural complications
Fall † 1	1/367 (0.27%)	1/368 (0.27%)
Device failure † 1	1/367 (0.27%)	0/368 (0.00%)
Femur fracture † 1	0/367 (0.00%)	1/368 (0.27%)
Hip fracture † 1	0/367 (0.00%)	1/368 (0.27%)
Mouth injury † 1	1/367 (0.27%)	0/368 (0.00%)
Muscle strain † 1	1/367 (0.27%)	0/368 (0.00%)
Procedural complication † 1	0/367 (0.00%)	1/368 (0.27%)
Traumatic brain injury † 1	1/367 (0.27%)	0/368 (0.00%)
Wound complication † 1	1/367 (0.27%)	0/368 (0.00%)
Investigations
Blood sodium decreased † 1	0/367 (0.00%)	1/368 (0.27%)
Heart rate increased † 1	1/367 (0.27%)	0/368 (0.00%)
Weight decreased † 1	0/367 (0.00%)	1/368 (0.27%)
Metabolism and nutrition disorders
Dehydration † 1	1/367 (0.27%)	6/368 (1.63%)
Failure to thrive † 1	1/367 (0.27%)	0/368 (0.00%)
Hypoglycaemia † 1	0/367 (0.00%)	1/368 (0.27%)
Hyponatraemia † 1	0/367 (0.00%)	1/368 (0.27%)
Hypovolaemia † 1	0/367 (0.00%)	1/368 (0.27%)
Musculoskeletal and connective tissue disorders
Arthralgia † 1	2/367 (0.54%)	0/368 (0.00%)
Back pain † 1	2/367 (0.54%)	0/368 (0.00%)
Musculoskeletal chest pain † 1	1/367 (0.27%)	0/368 (0.00%)
Neck pain † 1	0/367 (0.00%)	1/368 (0.27%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer † 1	1/367 (0.27%)	0/368 (0.00%)
Lung cancer metastatic † 1	0/367 (0.00%)	1/368 (0.27%)
Malignant pleural effusion † 1	0/367 (0.00%)	1/368 (0.27%)
Metastases to meninges † 1	0/367 (0.00%)	1/368 (0.27%)
Metastases to spine † 1	1/367 (0.27%)	0/368 (0.00%)
Myelodysplastic syndrome † 1	0/367 (0.00%)	1/368 (0.27%)
Nervous system disorders
Syncope † 1	1/367 (0.27%)	2/368 (0.54%)
Cerebral infarction † 1	1/367 (0.27%)	1/368 (0.27%)
Convulsion † 1	1/367 (0.27%)	1/368 (0.27%)
Embolic stroke † 1	0/367 (0.00%)	2/368 (0.54%)
Transient ischaemic attack † 1	1/367 (0.27%)	1/368 (0.27%)
Cerebellar infarction † 1	0/367 (0.00%)	1/368 (0.27%)
Cerebral artery embolism † 1	0/367 (0.00%)	1/368 (0.27%)
Cerebral ischaemia † 1	0/367 (0.00%)	1/368 (0.27%)
Cerebrovascular accident † 1	1/367 (0.27%)	0/368 (0.00%)
Cognitive disorder † 1	0/367 (0.00%)	1/368 (0.27%)
Cranial neuropathy † 1	1/367 (0.27%)	0/368 (0.00%)
Encephalopathy † 1	1/367 (0.27%)	0/368 (0.00%)
Headache † 1	0/367 (0.00%)	1/368 (0.27%)
Leukoencephalopathy † 1	0/367 (0.00%)	1/368 (0.27%)
Neuropathy peripheral † 1	1/367 (0.27%)	0/368 (0.00%)
Reversible posterior leukoencephalopathy syndrome † 1	0/367 (0.00%)	1/368 (0.27%)
Psychiatric disorders
Confusional state † 1	1/367 (0.27%)	5/368 (1.36%)
Hallucinations, mixed † 1	1/367 (0.27%)	0/368 (0.00%)
Mental status changes † 1	0/367 (0.00%)	1/368 (0.27%)
Psychotic disorder † 1	0/367 (0.00%)	1/368 (0.27%)
Renal and urinary disorders
Renal failure acute † 1	0/367 (0.00%)	1/368 (0.27%)
Urinary retention † 1	0/367 (0.00%)	1/368 (0.27%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea † 1	6/367 (1.63%)	2/368 (0.54%)
Haemoptysis † 1	1/367 (0.27%)	4/368 (1.09%)
Pleural effusion † 1	2/367 (0.54%)	2/368 (0.54%)
Respiratory failure † 1	1/367 (0.27%)	3/368 (0.82%)
Epistaxis † 1	0/367 (0.00%)	3/368 (0.82%)
Hypoxia † 1	2/367 (0.54%)	0/368 (0.00%)
Interstitial lung disease † 1	0/367 (0.00%)	2/368 (0.54%)
Pulmonary haemorrhage † 1	2/367 (0.54%)	0/368 (0.00%)
Bronchial haemorrhage † 1	1/367 (0.27%)	0/368 (0.00%)
Chronic obstructive pulmonary disease † 1	0/367 (0.00%)	1/368 (0.27%)
Obstructive airways disorder † 1	1/367 (0.27%)	0/368 (0.00%)
Pneumonitis † 1	0/367 (0.00%)	1/368 (0.27%)
Pulmonary embolism † 1	1/367 (0.27%)	0/368 (0.00%)
Vascular disorders
Deep vein thrombosis † 1	3/367 (0.82%)	3/368 (0.82%)
Haematoma † 1	1/367 (0.27%)	0/368 (0.00%)
Hypertension † 1	0/367 (0.00%)	1/368 (0.27%)
Hypotension † 1	0/367 (0.00%)	1/368 (0.27%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA (12.0)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Bevacizumab + Placebo	Bevacizumab + Erlotinib
	Affected / at Risk (%)	Affected / at Risk (%)
Total	288/367 (78.47%)	341/368 (92.66%)
Blood and lymphatic system disorders
Anaemia † 1	21/367 (5.72%)	19/368 (5.16%)
Gastrointestinal disorders
Abdominal pain † 1	12/367 (3.27%)	19/368 (5.16%)
Constipation † 1	33/367 (8.99%)	34/368 (9.24%)
Diarrhoea † 1	72/367 (19.62%)	188/368 (51.09%)
Nausea † 1	39/367 (10.63%)	75/368 (20.38%)
Stomatitis † 1	9/367 (2.45%)	27/368 (7.34%)
Vomiting † 1	26/367 (7.08%)	38/368 (10.33%)
General disorders
Asthenia † 1	12/367 (3.27%)	20/368 (5.43%)
Chest pain † 1	24/367 (6.54%)	18/368 (4.89%)
Fatigue † 2	91/367 (24.80%)	126/368 (34.24%)
Mucosal inflammation † 2	3/367 (0.82%)	26/368 (7.07%)
Pyrexia † 2	9/367 (2.45%)	20/368 (5.43%)
Infections and infestations
Urinary tract infection † 2	9/367 (2.45%)	23/368 (6.25%)
Investigations
Weight decreased † 2	21/367 (5.72%)	43/368 (11.68%)
Metabolism and nutrition disorders
Anorexia † 2	36/367 (9.81%)	76/368 (20.65%)
Musculoskeletal and connective tissue disorders
Arthralgia † 2	42/367 (11.44%)	20/368 (5.43%)
Back pain † 2	34/367 (9.26%)	39/368 (10.60%)
Musculoskeletal pain † 2	35/367 (9.54%)	28/368 (7.61%)
Pain in extremity † 2	23/367 (6.27%)	29/368 (7.88%)
Nervous system disorders
Dizziness † 2	18/367 (4.90%)	23/368 (6.25%)
Dysgeusia † 2	10/367 (2.72%)	23/368 (6.25%)
Headache † 2	45/367 (12.26%)	38/368 (10.33%)
Neuropathy peripheral † 2	25/367 (6.81%)	28/368 (7.61%)
Psychiatric disorders
Depression † 2	10/367 (2.72%)	32/368 (8.70%)
Insomnia † 2	13/367 (3.54%)	23/368 (6.25%)
Renal and urinary disorders
Proteinuria † 2	21/367 (5.72%)	24/368 (6.52%)
Respiratory, thoracic and mediastinal disorders
Cough † 2	66/367 (17.98%)	63/368 (17.12%)
Dysphonia † 2	21/367 (5.72%)	15/368 (4.08%)
Dyspnoea † 2	44/367 (11.99%)	42/368 (11.41%)
Epistaxis † 2	32/367 (8.72%)	40/368 (10.87%)
Oropharyngeal pain † 2	10/367 (2.72%)	19/368 (5.16%)
Skin and subcutaneous tissue disorders
Alopecia † 2	18/367 (4.90%)	26/368 (7.07%)
Dermatitis acneiform † 2	15/367 (4.09%)	58/368 (15.76%)
Dry skin † 2	23/367 (6.27%)	44/368 (11.96%)
Pruritus † 2	25/367 (6.81%)	21/368 (5.71%)
Rash † 2	69/367 (18.80%)	204/368 (55.43%)
Vascular disorders
Hypertension † 2	85/367 (23.16%)	87/368 (23.64%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA; 2 Term from vocabulary, MedDRA (12.0)

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

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.

Results Point of Contact

• Name/Title: Roche Trial Information Hotline
• Organization: F. Hoffmann-La Roche AG
• Phone: +41 616878333
• EMail: global.trial_information@roche.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Johnson BE, Kabbinavar F, Fehrenbacher L, Hainsworth J, Kasubhai S, Kressel B, Lin CY, Marsland T, Patel T, Polikoff J, Rubin M, White L, Yang JC, Bowden C, Miller V. ATLAS: randomized, double-blind, placebo-controlled, phase IIIB trial comparing bevacizumab therapy with or without erlotinib, after completion of chemotherapy, with bevacizumab for first-line treatment of advanced non-small-cell lung cancer. J Clin Oncol. 2013 Nov 1;31(31):3926-34. doi: 10.1200/JCO.2012.47.3983. Epub 2013 Oct 7.

• Responsible Party: Genentech, Inc.
• ClinicalTrials.gov Identifier: NCT00257608
• Other Study ID Numbers: AVF3671g; BO20800 ( Other Identifier: Hoffmann-La Roche )
• First Submitted: November 21, 2005
• First Posted: November 23, 2005
• Results First Submitted: November 9, 2015
• Results First Posted: March 15, 2016
• Last Update Posted: April 18, 2016