AVAPERL1 Study: A Study of Avastin (Bevacizumab) With or Without Pemetrexed as Maintenance Therapy After Avastin in First Line in Patients With Non-Squamous Non-Small Cell Lung Cancer

• ClinicalTrials.gov Identifier: NCT00961415
• Recruitment Status: Completed
• First Posted: August 19, 2009
• Results First Posted: February 22, 2016
• Last Update Posted: February 22, 2016
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Non-Squamous Non-Small Cell Lung Cancer
• Interventions: Drug: bevacizumab [Avastin]; Drug: cisplatin; Drug: pemetrexed
• Enrollment: 376

Participant Flow

Recruitment Details	A total of 414 participants were screened out of which 38 participants were excluded for not meeting the eligibility criteria, declining to participate, or for other reasons. A total of 376 participants were recruited over an 18-month period across 81 centers in 11 countries from 17 August 2009 to 3 May 2011.
Pre-assignment Details	Of the 376 participants enrolled in this study, 3 participants did not start induction phase treatment.

Arm/Group Title	Induction Treatment Phase	Bevacizumab Maintenance Treatment (Trt) Arm A	Bevacizumab +Pemetrexed Maintenance Trt Arm B
Arm/Group Description	Bevacizumab 7.5 milligram (mg)/ kilogram (kg) + cisplatin 75 mg/m^2 + pemetrexed 500 mg/m^2 was administered intravenously (IV) every 3 weeks. Participants received 4 cycles of induction therapy.	Bevacizumab 7.5 mg/kg was administered IV every 3 weeks until progression of disease, unacceptable toxicity, or withdrawal of consent. The first cycle of maintenance therapy was to be administered a maximum of 4 weeks after the fourth cycle of induction therapy.	Bevacizumab 7.5 mg/kg + pemetrexed 500 mg/m^2 was administered IV every 3 weeks until progression of disease, unacceptable toxicity, or withdrawal of consent. Pemetrexed-treated participants received standard supplementation with folic acid orally (350 to 1000 microgram [mcg] daily), vitamin B12 intramuscularly (1000 mcg every 3 cycles), and dexamethasone prophylaxis orally (4 mg twice a day) on Days -1, 1, and 2 of each cycle. The first cycle of maintenance therapy was to be administered a maximum of 4 weeks after the fourth cycle of induction therapy.
Period Title: Induction Treatment Phase
Started	376	0	0
Completed	253	0	0
Not Completed	123	0	0
Reason Not Completed
Withdrawal by Subject	11	0	0
Death	77	0	0
Protocol Violation	1	0	0
Physician Decision	2	0	0
Didn't meet maintenance phase criteria	27	0	0
Other Reason	5	0	0
Period Title: Maintenance Treatment Phase
Started	0	125	128
Completed	0	77	83
Not Completed	0	48	45
Reason Not Completed
Death	0	42	34
Investigators decision	0	2	0
Withdrawal by Subject	0	3	8
Other reason	0	1	3

Baseline Characteristics

Arm/Group Title		Bevacizumab Maintenance Trt Arm A	Bevacizumab +Pemetrexed Maintenance Trt Arm B	Total
Arm/Group Description		Bevacizumab 7.5 mg/kg was administered IV every 3 weeks until progression of disease, unacceptable toxicity, or withdrawal of consent. The first cycle of maintenance therapy had to be administered a maximum of 4 weeks after the fourth cycle of induction therapy.	Bevacizumab 7.5 mg/kg + pemetrexed 500 mg/m^2 was administered IV every 3 weeks until progression of disease, unacceptable toxicity, or withdrawal of consent. Pemetrexed-treated participants received standard supplementation with folic acid orally (350 to 1000 microgram [mcg] daily), vitamin B12 intramuscularly (1000 mcg every 3 cycles), and dexamethasone prophylaxis orally (4 mg twice a day) on Days -1, 1, and 2 of each cycle. The first cycle of maintenance therapy was to be administered a maximum of 4 weeks after the fourth cycle of induction therapy.	Total of all reporting groups
Overall Number of Baseline Participants		125	128	253
Baseline Analysis Population Description		The Intent-to-treat (ITT) population included all the participants that were randomized.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	125 participants	128 participants	253 participants
		59.5 (8.25)	59.3 (8.86)	59.4 (8.55)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	125 participants	128 participants	253 participants
	Female	55 44.0%	54 42.2%	109 43.1%
	Male	70 56.0%	74 57.8%	144 56.9%

Outcome Measures

1. Primary Outcome

Title	Progression Free Survival During Maintenance Treatment Phase
Description	Progression free survival (PFS) is defined as the time from randomization to the date of documented disease progression according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1) , or the date of occurrence of a second primary cancer, or date of death from any cause, whichever comes first. Progression is defined using (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, the appearance of new lesions and increase of at least 5 mm in the sum of diameters of target lesions.Tumor assessment was done before Cycle 3, at Cycle 2 of maintenance therapy and every nine weeks thereafter.
Time Frame	Up to 21 months

Outcome Measure Data

Analysis Population Description

The ITT population included all the participants that were randomized.

Arm/Group Title	Bevacizumab Maintenance Trt Arm A	Bevacizumab +Pemetrexed Maintenance Trt Arm B
Arm/Group Description:	Bevacizumab 7.5 mg/kg was administered IV every 3 weeks until progression of disease, unacceptable toxicity, or withdrawal of consent. The first cycle of maintenance therapy had to be administered a maximum of 4 weeks after the fourth cycle of induction therapy.	Bevacizumab 7.5 mg/kg + pemetrexed 500 mg/m^2 was administered IV every 3 weeks until progression of disease, unacceptable toxicity, or withdrawal of consent. Pemetrexed-treated participants received standard supplementation with folic acid orally (350 to 1000 microgram [mcg] daily), vitamin B12 intramuscularly (1000 mcg every 3 cycles), and dexamethasone prophylaxis orally (4 mg twice a day) on Days -1, 1, and 2 of each cycle. The first cycle of maintenance therapy was to be administered a maximum of 4 weeks after the fourth cycle of induction therapy.
Overall Number of Participants Analyzed	125	128
Median (95% Confidence Interval); Unit of Measure: Months
	6.6; (6.0 to 7.8)	10.2; (9.1 to 11.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bevacizumab Maintenance Trt Arm A, Bevacizumab +Pemetrexed Maintenance Trt Arm B
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.50
	Confidence Interval	(2-Sided) 95%; 0.37 to 0.69
	Estimation Comments	[Not Specified]

2. Secondary Outcome

Title	Overall Survival During Maintenance Treatment Phase
Description	Overall survival (OS) is assessed from the date of first induction treatment until the date of death. Tumor assessment was done before Cycle 3, at Cycle 2 of maintenance therapy and every nine weeks thereafter.
Time Frame	Up to 21 months

Outcome Measure Data

Analysis Population Description

The ITT population included all the participants that were randomized.

Arm/Group Title	Bevacizumab Maintenance Trt Arm A	Bevacizumab +Pemetrexed Maintenance Trt Arm B
Arm/Group Description:	Bevacizumab 7.5 mg/kg was administered IV every 3 weeks until progression of disease, unacceptable toxicity, or withdrawal of consent. The first cycle of maintenance therapy had to be administered a maximum of 4 weeks after the fourth cycle of induction therapy.	Bevacizumab 7.5 mg/kg + pemetrexed 500 mg/m^2 was administered IV every 3 weeks until progression of disease, unacceptable toxicity, or withdrawal of consent. Pemetrexed-treated participants received standard supplementation with folic acid orally (350 to 1000 microgram [mcg] daily), vitamin B12 intramuscularly (1000 mcg every 3 cycles), and dexamethasone prophylaxis orally (4 mg twice a day) on Days -1, 1, and 2 of each cycle. The first cycle of maintenance therapy was to be administered a maximum of 4 weeks after the fourth cycle of induction therapy.
Overall Number of Participants Analyzed	125	128
Median (95% Confidence Interval); Unit of Measure: Months
	15.7 [1]; (14.3 to NA)	NA [1]; (NA to NA)

[1]

Data unavailable, as the follow-up time was very short to observe enough survival events.

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bevacizumab Maintenance Trt Arm A, Bevacizumab +Pemetrexed Maintenance Trt Arm B
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.230
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.75
	Confidence Interval	(2-Sided) 95%; 0.47 to 1.20
	Estimation Comments	[Not Specified]

3. Secondary Outcome

Title	Best Overall Response Rate During Maintenance Treatment Phase
Description	The best overall response rate (BORR) is defined as the percentage of participants having achieved confirmed Complete Response (CR) and Partial Response (PR) as the best overall response. CR was defined as complete disappearance of all target lesions and non-target disease. PR was defined as a greater than or equal to (≥) 30% decrease under baseline of the sum of diameters of all target lesions. Stable disease (SD) is defined as steady state of disease with neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD).Tumor assessment was done before Cycle 3, at Cycle 2 of maintenance therapy and every nine weeks thereafter.
Time Frame	Up to 21 months

Outcome Measure Data

Analysis Population Description

The ITT population which included all the participants that were randomized.

Arm/Group Title	Bevacizumab Maintenance Trt Arm A	Bevacizumab +Pemetrexed Maintenance Trt Arm B
Arm/Group Description:	Bevacizumab 7.5 mg/kg was administered IV every 3 weeks until progression of disease, unacceptable toxicity, or withdrawal of consent. The first cycle of maintenance therapy had to be administered a maximum of 4 weeks after the fourth cycle of induction therapy.	Bevacizumab 7.5 mg/kg + pemetrexed 500 mg/m^2 was administered IV every 3 weeks until progression of disease, unacceptable toxicity, or withdrawal of consent. Pemetrexed-treated participants received standard supplementation with folic acid orally (350 to 1000 microgram [mcg] daily), vitamin B12 intramuscularly (1000 mcg every 3 cycles), and dexamethasone prophylaxis orally (4 mg twice a day) on Days -1, 1, and 2 of each cycle. The first cycle of maintenance therapy was to be administered a maximum of 4 weeks after the fourth cycle of induction therapy.
Overall Number of Participants Analyzed	125	128
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
Partial response (PR)	50; (40.9 to 59.1)	55.5; (46.4 to 64.3)
Stable disease (SD)	50; (40.9 to 59.1)	44.5; (35.7 to 53.6)

4. Secondary Outcome

Title	Duration of Response During Maintenance Treatment Phase
Description	Duration of response is defined as the time in months from the initial start of response PR or better to the earlier of documented PD or death due to any cause. Participants who had neither progressed nor died at the date of clinical cutoff, who withdrew from the study, were lost to follow-up, or were without documented disease progression were censored at the date of the last available tumor assessment. The analysis was based on all participants with measurable disease at baseline who achieved response.Tumor assessment was done before Cycle 3, at Cycle 2 of maintenance therapy and every nine weeks thereafter.
Time Frame	Up to 21 months

Outcome Measure Data

Analysis Population Description

The ITT population included all the participants that were randomized.Participants available at particular time point for assessment were included in the analysis.

Arm/Group Title	Bevacizumab Maintenance Trt Arm A	Bevacizumab +Pemetrexed Maintenance Trt Arm B
Arm/Group Description:	Bevacizumab 7.5 mg/kg was administered IV every 3 weeks until progression of disease, unacceptable toxicity, or withdrawal of consent. The first cycle of maintenance therapy had to be administered a maximum of 4 weeks after the fourth cycle of induction therapy.	Bevacizumab 7.5 mg/kg + pemetrexed 500 mg/m^2 was administered IV every 3 weeks until progression of disease, unacceptable toxicity, or withdrawal of consent. Pemetrexed-treated participants received standard supplementation with folic acid orally (350 to 1000 microgram [mcg] daily), vitamin B12 intramuscularly (1000 mcg every 3 cycles), and dexamethasone prophylaxis orally (4 mg twice a day) on Days -1, 1, and 2 of each cycle. The first cycle of maintenance therapy was to be administered a maximum of 4 weeks after the fourth cycle of induction therapy.
Overall Number of Participants Analyzed	62	71
Median (95% Confidence Interval); Unit of Measure: Months
	5.7; (4.9 to 7.2)	9.2; (6.8 to 10.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bevacizumab Maintenance Trt Arm A, Bevacizumab +Pemetrexed Maintenance Trt Arm B
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.006
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.53
	Confidence Interval	(2-Sided) 95%; 0.34 to 0.84
	Estimation Comments	[Not Specified]

5. Secondary Outcome

Title	Duration of Disease Control During Maintenance Treatment Phase
Description	Duration of disease control is defined as the time in months from randomization to the earlier of documented PD or death due to any cause. Tumor assessment was done before Cycle 3, at Cycle 2 of maintenance therapy and every nine weeks thereafter.
Time Frame	Up to 21 months

Outcome Measure Data

Analysis Population Description

The ITT population included all the participants that were randomized.

Arm/Group Title	Bevacizumab Maintenance Trt Arm A	Bevacizumab +Pemetrexed Maintenance Trt Arm B
Arm/Group Description:	Bevacizumab 7.5 mg/kg was administered IV every 3 weeks until progression of disease, unacceptable toxicity, or withdrawal of consent. The first cycle of maintenance therapy had to be administered a maximum of 4 weeks after the fourth cycle of induction therapy.	Bevacizumab 7.5 mg/kg + pemetrexed 500 mg/m^2 was administered IV every 3 weeks until progression of disease, unacceptable toxicity, or withdrawal of consent. Pemetrexed-treated participants received standard supplementation with folic acid orally (350 to 1000 microgram [mcg] daily), vitamin B12 intramuscularly (1000 mcg every 3 cycles), and dexamethasone prophylaxis orally (4 mg twice a day) on Days -1, 1, and 2 of each cycle. The first cycle of maintenance therapy was to be administered a maximum of 4 weeks after the fourth cycle of induction therapy.
Overall Number of Participants Analyzed	125	128
Median (95% Confidence Interval); Unit of Measure: Months
	4.9; (3.9 to 5.7)	7.8; (6.8 to 9.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bevacizumab Maintenance Trt Arm A, Bevacizumab +Pemetrexed Maintenance Trt Arm B
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.52
	Confidence Interval	(2-Sided) 95%; 0.38 to 0.70
	Estimation Comments	[Not Specified]

6. Secondary Outcome

Title	Incidence of Adverse Events and Serious Adverse Event
Description	An adverse events (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not considered related to the medicinal (investigational) product. An serious adverse event (SAE) is any experience that suggests a significant hazard, contraindication, side effect, or precaution.
Time Frame	Up to 21 months

Outcome Measure Data

Analysis Population Description

The safety population comprised of all participants who received at least one dose of study medication. Participants who received induction treatment and were not randomised to maintenance treatment are also included in analysis.

Arm/Group Title	Bevacizumab Maintenance Trt Arm A	Bevacizumab +Pemetrexed Maintenance Trt Arm B	No Maintenance Trt
Arm/Group Description:	Bevacizumab 7.5 mg/kg was administered IV every 3 weeks until progression of disease, unacceptable toxicity, or withdrawal of consent. Among the 125 participants allocated to Bevacizumab Maintenance Trt Arm A, five participants did not receive treatment so they were excluded from analysis.	Bevacizumab 7.5 mg/kg + pemetrexed 500mg/m^2 was administered IV every 3 weeks until progression of disease, unacceptable toxicity, or withdrawal of consent. Among the 128 participants allocated to Bevacizumab +Pemetrexed Maintenance Trt Arm B, three participants did not receive treatment so they were excluded from analysis.	A total of 128 participants were not randomized to maintenance therapy because of discontinuations related to an AE, progressive disease, withdrawal of consent, or other reasons. Five participants in Bevacizumab Maintenance Trt Arm A and three in Bevacizumab +Pemetrexed Maintenance Trt Arm B, respectively, did not receive maintenance treatment so they were also included in the not randomized arm.
Overall Number of Participants Analyzed	120	125	128
Measure Type: Number; Unit of Measure: Participants
AE	116	123	119
SAE	26	42	70

7. Secondary Outcome

Title	Number of Participants With Marked Laboratory Abnormalities
Description	Marked laboratory abnormalities were defined as those values that were outside the reference range and showed a clinically relevant change from Baseline. The reference range for Platelets was 100-550 (10^9/L), for White blood cells (WBC) was 3.0-18.0 (10^9/L), for Lymphocytes was 0.70-7.60 (10^9/L), and Neutrophil 1.50-9.25 (10^9/L ).
Time Frame	Up to 21 months

Outcome Measure Data

Analysis Population Description

The safety population comprised of all participants who received at least one dose of study medication. Participants who received induction treatment and were not randomised to maintenance treatment are also included in analysis.

Arm/Group Title	Bevacizumab Maintenance Trt Arm A	Bevacizumab +Pemetrexed Maintenance Trt Arm B	No Maintenance Trt
Arm/Group Description:	Bevacizumab 7.5 mg/kg was administered IV every 3 weeks until progression of disease, unacceptable toxicity, or withdrawal of consent. Among the 125 participants allocated to Bevacizumab Maintenance Trt Arm A, five participants did not receive treatment so they were excluded from analysis.	Bevacizumab 7.5 mg/kg + pemetrexed 500mg/m^2 was administered IV every 3 weeks until progression of disease, unacceptable toxicity, or withdrawal of consent. Among the 128 participants allocated to Bevacizumab +Pemetrexed Maintenance Trt Arm B, three participants did not receive treatment so they were excluded from analysis..	A total of 128 participants were not randomized to maintenance therapy because of discontinuations related to an AE, progressive disease, withdrawal of consent, or other reasons. Five participants in Bevacizumab Maintenance Trt Arm A and three in Bevacizumab +Pemetrexed Maintenance Trt Arm B, respectively, did not receive maintenance treatment so they were also included in the not randomized arm...
Overall Number of Participants Analyzed	120	125	128
Measure Type: Number; Unit of Measure: Participants
Alanine amino transferase (ALT)	18	26	8
Aspartate amino transferase (AST)	18	26	8
Alkaline phosphatase	18	26	8
Hemoglobin	28	30	25
International normalized ratio (INR)	1	0	0
Lymphocytes	28	30	25
Neutrophils	28	30	25
Platelets	28	30	25
Serum creatinine	18	26	8
WBC	28	30	25
Activated partial thromboplastin time (aPTT)	1	0	0

8. Secondary Outcome

Title	Quality of Life
Description	European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire-Cancer 30 (EORTC QLQ-C30): included functional scales (physical, role, cognitive, emotional, and social), global health status, symptom scales (fatigue, pain, nausea/vomiting) and single items (dyspnoea, appetite loss, insomnia, constipation/diarrhea and financial difficulties). The European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire-Lung Cancer 13 [EORTC QLQ-LC13]consisted of 1 multi-item scale and 9 single items that assessed the specific symptoms (dyspnea, cough, hemoptysis, and site specific pain), side effects (sore mouth, dysphagia, neuropathy, and alopecia), and pain medication use of lung cancer participants receiving chemotherapy. Scale score range: 0 to 100. Higher symptom score = greater degree of symptom severity. QOL was assessed using Pre-Induction Baseline (Pre-ind BL), Maintenance (MTC), End of study (EOS) cycles.
Time Frame	Up to 21 months

Outcome Measure Data

Analysis Population Description

The ITT population included all the participants that were randomized.

Arm/Group Title	Bevacizumab Maintenance Trt Arm A	Bevacizumab +Pemetrexed Maintenance Trt Arm B
Arm/Group Description:	Bevacizumab 7.5 mg/kg was administered IV every 3 weeks until progression of disease, unacceptable toxicity, or withdrawal of consent. The first cycle of maintenance therapy had to be administered a maximum of 4 weeks after the fourth cycle of induction therapy	Bevacizumab 7.5 mg/kg + pemetrexed 500 mg/m^2 was administered IV every 3 weeks until progression of disease, unacceptable toxicity, or withdrawal of consent. Pemetrexed-treated participants received standard supplementation with folic acid orally (350 to 1000 mcg daily), vitamin B12 intramuscularly (1000 mcg every 3 cycles), and dexamethasone prophylaxis orally (4 mg twice a day) on Days -1, 1, and 2 of each cycle. The first cycle of maintenance therapy was to be administered a maximum of 4 weeks after the fourth cycle of induction therapy.
Overall Number of Participants Analyzed	125	128
Mean (Standard Deviation); Unit of Measure: Score on scale
[Pre-ind BL] Global Health Status Scale n=116,121	57.9 (23.90)	59.7 (21.74)
[Pre-ind BL] Physical Functional Scale (n=118,121)	74.8 (23.69)	79.4 (18.09)
[Pre-ind BL] Role Functional Scale (n=118,121)	68.4 (32.50)	71.1 (28.28)
[Pre-ind BL] Emotional Functional Scale n=117,121	71.7 (21.93)	69.8 (21.97)
[Pre-ind BL] Cognitive Functional Scale n=117,121	86.0 (21.55)	88.0 (16.70)
[Pre-ind BL]] Social Functional Scale (n=116,120)	79.3 (25.60)	78.7 (26.10)
[Pre-ind BL] Fatigue Symptom Scale (n=118,121)	33.3 (27.18)	31.5 (21.73)
[Pre-ind BL] Nausea & Vomiting Scale n=118,121	7.2 (17.50)	4.3 (12.46)
[Pre-ind BL] Pain Symptom Scale (n=118,121)	36.7 (31.92)	24.7 (26.88)
[Pre-ind BL] Dyspnea Symptom Scale (n=118,121)	29.7 (30.75)	30.6 (29.69)
[Pre-ind BL] Insomnia Symptom Scale n=118,121	33.3 (34.59)	33.9 (30.42)
[Pre-ind BL] Appetite Loss Symptom Scale n=118,121	19.2 (30.01)	18.7 (29.15)
[Pre-ind BL]] Constipation Symptom Scale n=118,121	18.6 (30.68)	9.1 (20.18)
[Pre-ind BL] Diarrhea Symptom Scale (n=117,121)	7.1 (17.96)	5.2 (14.91)
[Pre-ind BL]Financial Difficulties Scale n=114,120	17.3 (30.48)	17.2 (29.62)
[MTC Cycle 3]Global Health Status (n=69,87)	63.3 (20.02)	58.6 (19.71)
[MTC Cycle 3]Physical Functional Scale (n=69,87)	77.1 (20.72)	76.0 (20.37)
[MTC Cycle 3]Role Functional Scale (n=69,87)	74.2 (27.79)	69.9 (28.51)
[MTC Cycle 3]Emotional Functional Scale (n=69,87)	82.5 (19.86)	78.4 (18.48)
[MTC Cycle 3]Cognitive Functional Scale (n=69,87)	84.3 (23.20)	82.6 (19.17)
[MTC Cycle 3]Social Functional Scale (n=69,87)	82.1 (25.62)	73.0 (24.28)
[MTC Cycle 3]Fatigue Symptom Scale (n=69,87)	32.1 (22.88)	34.5 (21.50)
[MTC Cycle 3]Nausea and Vomiting Scale (n=69,87)	7.2 (16.78)	8.8 (12.92)
[MTC Cycle 3]Pain Symptom Scale (n=69,87)	23.9 (27.64)	17.4 (21.85)
[MTC Cycle 3]Dyspnea Symptom Scale (n=69,87)	26.1 (27.93)	29.9 (26.91)
MTC Cycle 3]Appetite Loss Symptom Scale (n=69,87)	13.5 (22.37)	18.4 (25.80)
[MTC Cycle 3]Insomnia Symptom Scale (n=69,87)	19.3 (24.53)	19.5 (25.19)
[MTC Cycle 3]Constipation Symptom Scale (n=69,87)	10.1 (19.22)	11.1 (20.12)
[MTC Cycle 3]Diarrhea Symptom Scale (n=69,87)	3.4 (12.97)	5.7 (14.56)
[MTC Cycle 3]Financial Difficulties Scale (n=68,86	18.1 (27.88)	19.4 (26.30)
[MTC Cycle 5] Global Health Status (n=51,77)	63.2 (20.36)	62.9 (18.81)
[MTC Cycle 5] Physical Functional Scale (n=51,77)	78.7 (21.29)	78.4 (15.45)
[MTC Cycle 5] Role Functional Scale (n=51,77)	74.5 (31.15)	68.8 (27.08)
[MTC Cycle 5] Emotional Functional Scale (n=51,77)	78.8 (23.76)	78.7 (20.96)
[MTC Cycle 5] Cognitive Functional Scale (n=51,77)	81.0 (26.04)	84.6 (18.09)
[MTC Cycle 5] Social Functional Scale (n=51,77)	85.3 (22.52)	77.9 (22.85)
[MTC Cycle 5] Fatigue Symptom Scale (n=51,77)	32.2 (23.01)	34.5 (22.12)
[MTC Cycle 5] Nausea and Vomiting Scale (n=51,77)	9.2 (18.05)	10.0 (20.10)
[MTC Cycle 5] Pain Symptom Scale (n=51,77)	23.5 (26.28)	20.1 (25.27)
[MTC Cycle 5] Dyspnea Symptom Scale (n=51,77)	25.5 (27.96)	35.9 (30.95)
[MTC Cycle 5] Insomnia Symptom Scale( n=51,77)	21.6 (28.92)	22.1 (27.36)
MTC Cycle 5] Appetite Loss Symptom Scale (n=51,77)	10.5 (19.43)	19.9 (26.63)
[MTC Cycle 5] Constipation Symptom Scale (n=51,77)	9.2 (20.09)	17.3 (29.42)
[MTC Cycle 5] Diarrhea Symptom Scale (n=51,77)	10.5 (20.54)	2.6 (8.99)
[MTC Cycle 5] Financial Difficulties Scale n=50,77	16.0 (28.76)	17.7 (23.31)
[MTC Cycle 7] Global Health Status Scale (n=38,64)	61.2 (21.69)	61.3 (19.55)
[MTC Cycle 7] Physical Functional Scale (n=38,64)	75.6 (21.49)	74.7 (19.38)
[MTC Cycle 7]Role Functional Scale (n=38,64)	76.8 (24.97)	70.8 (28.79)
[MTC Cycle 7]Emotional Functional Scale (n=38,64)	81.6 (22.27)	77.5 (18.64)
[MTC Cycle 7]Cognitive Functional Scale (n=38,64)	77.2 (27.51)	81.0 (18.98)
[MTC Cycle 7]Social Functional Scale (n=38,64)	82.9 (24.35)	72.1 (28.65)
[MTC Cycle 7]Fatigue Symptom Scale (n=38,64)	32.3 (22.07)	33.7 (24.72)
[MTC Cycle 7]Nausea & Vomiting Scale (n=38,64)	8.3 (18.88)	9.6 (16.48)
[MTC Cycle 7]Pain Symptom Scale (n=38,64)	21.5 (23.86)	19.8 (23.55)
[MTC Cycle 7]Dyspnea Symptom Scale (n=38,64)	28.1 (26.31)	37 (32.59)
[MTC Cycle 7]Insomnia Symptom Scale (n=38,64)	16.7 (26.57)	28.6 (30.21)
[MTC Cycle 7]Appetite Loss Scale (n=38,64)	12.3 (21.11)	21.4 (29.32)
[MTC Cycle 7]Constipation Symptom Scale (n=38,64)	14 (28.61)	17.2 (24.48)
[MTC Cycle 7]Diarrhea Symptom Scale (n=38,64)	8.8 (20.04)	8.9 (21.61)
[MTC Cycle 7]Financial Difficulties Scale n=38,64	14.0 (24.05)	20.3 (27.61)
[MTC Cycle 9 ]Global Health Status Scale (n=33,50)	60.6 (18.67)	61.2 (17.71)
[MTC Cycle 9 ]Physical Functional Scale (n=33,50)	80.8 (20.53)	74.9 (19.54)
[MTC Cycle 9 ]Role Functional Scale (n=33,50)	75.8 (24.33)	69.7 (28.51)
[MTC Cycle 9 ]Emotional Functional Scale (n=33,50)	82.3 (18.61)	75 (22.46)
[MTC Cycle 9 ]Cognitive Functional Scale (n=33,50)	83.3 (20.41)	81.7 (19.99)
[MTC Cycle 9 ]Social Functional Scale (n=33,50)	83.8 (24.47)	71.7 (26.78)
[MTC Cycle 9 ]Fatigue Symptom Scale (n=33,50)	28.3 (24.07)	35.1 (25.03)
[MTC Cycle 9 ]Nausea & Vomiting Symptom (n=33,50)	5.1 (12.14)	12.0 (20.77)
[MTC Cycle 9 ]Pain Symptom Scale (n=33,50)	25.8 (30.93)	18.7 (21.47)
[MTC Cycle 9 ]Dyspnea Symptom Scale (n=32,50)	25.0 (25.40)	35.3 (27.28)
[MTC Cycle 9 ]Insomnia Symptom Scale (n=33,49)	23.2 (26.98)	30.6 (33.91)
[MTC Cycle 9 ]Appetite Loss Scale (n=33,50)	10.1 (19.52)	23.3 (29.55)
[MTC Cycle 9 ]Constipation Symptom Scale (n=33,50)	13.1 (24.92)	16.0 (25.41)
[MTC Cycle 9 ]Diarrhea Symptom Scale (n=33,50)	7.1 (20)	7.3 (18.18)
[MTC Cycle 9]Financial Difficulties Scale n=33,50	15.2 (23.70)	22.0 (27.45)
[MTC Cycle 11 ] Global Health Status Scale n=25,37	57.7 (18.93)	59.9 (21.41)
[MTC Cycle 11 ]Physical Functional Scale (n=25,37)	79.2 (16.48)	81.1 (17.81)
[MTC Cycle 11 ]Role Functional Scale (n=25,37)	77.3 (18.56)	73.9 (27.37)
[MTC Cycle 11 ]Emotional Functional Scale n=25,37	78.3 (19.09)	80.0 (19.88)
[MTC Cycle 11 ]Cognitive Functional Scale n=25,37	81.3 (26.49)	84.2 (17.10)
[MTC Cycle 11 ]Social Functional Scale (n=25,37)	84.7 (19.20)	77.9 (27.51)
[MTC Cycle 11 ]Fatigue Symptom Scale (n=25,37)	32.4 (22.20)	31.2 (20.92)
[MTC Cycle 11 ]Nausea & Vomiting Scale (n=25,37)	6.7 (15.96)	9.5 (18.23)
[MTC Cycle 11 ]Pain Symptom Scale (n=25,37)	29.3 (28.98)	19.8 (27.45)
[MTC Cycle 11 ]Dyspnea Symptom Scale (n=25,37)	30.7 (16.44)	28.8 (27.40)
[MTC Cycle 11 ]Insomnia Symptom Scale (n=25,37)	20.0 (23.57)	18.9 (26.69)
[MTC Cycle 11 ]Appetite Loss Scale (n=25,37)	9.3 (20.46)	18 (26.75)
MTC Cycle 11 ]Constipation Symptom Scale( n=25,37)	6.7 (13.61)	17.1 (24.37)
[MTC Cycle 11 ]Diarrhea Symptom Scale ( n=25,37)	1.3 (6.67)	7.2 (15.98)
[MTC Cycle 11]Financial Difficulties Scale n=24,37	15.3 (25.97)	18.0 (26.75)
[EOS]Global Health Status Scale (n=123,127)	55.1 (20.62)	57.2 (20.01)
[EOS]Physical Functional Scale (n=125,127)	70.2 (23.49)	72.5 (22.06)
[EOS]Role Functional Scale (n=125,127)	63.5 (32.43)	64.3 (29.68)
[EOS]Emotional Functional Scale (n=124,127)	74.4 (21.36)	77.3 (20.20)
[EOS]Cognitive Functional Scale ( n=124,127)	79.3 (24.91)	83.5 (19.30)
[EOS]Social Functional Scale (n=124,127)	73.3 (29.28)	72.6 (27.90)
[EOS]Fatigue Symptom Scale (n=125,127)	41.0 (26.42)	37.6 (23.80)
[EOS]Nausea & Vomiting Scale (n=125,127)	14.4 (23.70)	12.3 (20.70)
[EOS]Pain Symptom Scale (n=125,127)	30.4 (30.31)	21.1 (25.58)
[EOS]Dyspnea Symptom Scale (n=124,127)	31.5 (29.85)	34.1 (29.83)
[EOS]Insomnia Symptom Scale( n=125,127)	27.2 (26.57)	22.6 (28.45)
[EOS]Appetite Loss Symptom Scale (n=125,127)	26.9 (31.31)	26.0 (30.26)
[EOS]Constipation Symptom Scale (n=125,127)	17.6 (25.60)	12.1 (21.28)
[EOS]Diarrhea Symptom Scale(n=124,127)	9.7 (20.72)	6.8 (15.34)
[EOS]Financial Difficulties Scale (n=123,126)	16.8 (27.45)	16.9 (27.24)

Adverse Events

Time Frame	Up to 21 months (throughout the study)
Adverse Event Reporting Description	Serious adverse events and non-serious adverse events are reported in Safety Analysis Set, which consists of all participants who received at least one dose of study medication and had a safety assessment performed post baseline.
Arm/Group Title	No Maintenance Treatment	Maintenance Treatment Arm A	Maintenance Treatment Arm B
Arm/Group Description	A total of 128 participants were not randomized to maintenance therapy because of discontinuations related to an AE, progressive disease, withdrawal of consent, or other reasons. Five participants in Bevacizumab Maintenance Trt Arm A and three in Bevacizumab +Pemetrexed Maintenance Trt Arm B, respectively, did not receive maintenance treatment so they were also included in the not randomized arm..	Bevacizumab 7.5 mg/kg was administered IV every 3 weeks until progression of disease, unacceptable toxicity, or withdrawal of consent. Among the 125 participants allocated to Bevacizumab Maintenance Trt Arm A, five participants did not receive treatment so they were excluded from analysis	Bevacizumab 7.5 mg/kg + pemetrexed 500mg/m^2 was administered IV every 3 weeks until progression of disease, unacceptable toxicity, or withdrawal of consent. Among the 128 participants allocated to Bevacizumab +Pemetrexed Maintenance Trt Arm B, three participants did not receive treatment so they were excluded from analysis..
All-Cause Mortality
	No Maintenance Treatment	Maintenance Treatment Arm A	Maintenance Treatment Arm B
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--	--/--
Serious Adverse Events
	No Maintenance Treatment	Maintenance Treatment Arm A	Maintenance Treatment Arm B
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	70/128 (54.69%)	26/120 (21.67%)	42/125 (33.60%)
Blood and lymphatic system disorders
Anaemia † 1	4/128 (3.13%)	0/120 (0.00%)	1/125 (0.80%)
Neutropenia † 1	7/128 (5.47%)	0/120 (0.00%)	0/125 (0.00%)
Febrile neutropenia † 1	1/128 (0.78%)	1/120 (0.83%)	1/125 (0.80%)
Pancytopenia † 1	1/128 (0.78%)	1/120 (0.83%)	0/125 (0.00%)
Thrombocytopenia † 1	2/128 (1.56%)	0/120 (0.00%)	0/125 (0.00%)
Febrile bone marrow aplasia † 1	1/128 (0.78%)	0/120 (0.00%)	0/125 (0.00%)
Cardiac disorders
Myocardial infarction † 1	1/128 (0.78%)	0/120 (0.00%)	1/125 (0.80%)
Cardiac asthma † 1	1/128 (0.78%)	0/120 (0.00%)	0/125 (0.00%)
Cardiac failure † 1	1/128 (0.78%)	0/120 (0.00%)	0/125 (0.00%)
Cardiogenic shock † 1	1/128 (0.78%)	0/120 (0.00%)	0/125 (0.00%)
Cardiomyopathy † 1	0/128 (0.00%)	1/120 (0.83%)	0/125 (0.00%)
Pericardial effusion † 1	1/128 (0.78%)	0/120 (0.00%)	0/125 (0.00%)
Eye disorders
Vitreous detachment † 1	0/128 (0.00%)	0/120 (0.00%)	1/125 (0.80%)
Gastrointestinal disorders
Diarrhoea † 1	2/128 (1.56%)	2/120 (1.67%)	2/125 (1.60%)
Nausea † 1	0/128 (0.00%)	2/120 (1.67%)	3/125 (2.40%)
Vomiting † 1	1/128 (0.78%)	2/120 (1.67%)	0/125 (0.00%)
Abdominal pain † 1	0/128 (0.00%)	1/120 (0.83%)	1/125 (0.80%)
Abdominal pain upper † 1	0/128 (0.00%)	1/120 (0.83%)	1/125 (0.80%)
Constipation † 1	1/128 (0.78%)	0/120 (0.00%)	1/125 (0.80%)
Gastric haemorrhage † 1	1/128 (0.78%)	0/120 (0.00%)	0/125 (0.00%)
Gastrointestinal toxicity † 1	1/128 (0.78%)	0/120 (0.00%)	0/125 (0.00%)
Intestinal ischaemia † 1	1/128 (0.78%)	0/120 (0.00%)	0/125 (0.00%)
Oesophageal perforation † 1	1/128 (0.78%)	0/120 (0.00%)	0/125 (0.00%)
Pancreatitis † 1	1/128 (0.78%)	0/120 (0.00%)	0/125 (0.00%)
Rectal haemorrhage † 1	0/128 (0.00%)	1/120 (0.83%)	0/125 (0.00%)
Tongue oedema † 1	0/128 (0.00%)	0/120 (0.00%)	1/125 (0.80%)
General disorders
General physical health deterioration † 1	3/128 (2.34%)	1/120 (0.83%)	0/125 (0.00%)
Asthenia † 1	1/128 (0.78%)	1/120 (0.83%)	1/125 (0.80%)
Death † 1	2/128 (1.56%)	0/120 (0.00%)	1/125 (0.80%)
Malaise † 1	2/128 (1.56%)	0/120 (0.00%)	1/125 (0.80%)
Pain † 1	1/128 (0.78%)	0/120 (0.00%)	1/125 (0.80%)
Pyrexia † 1	1/128 (0.78%)	0/120 (0.00%)	1/125 (0.80%)
Sudden death † 1	2/128 (1.56%)	0/120 (0.00%)	0/125 (0.00%)
Fatigue † 1	1/128 (0.78%)	0/120 (0.00%)	0/125 (0.00%)
Haemorrhagic cyst † 1	0/128 (0.00%)	1/120 (0.83%)	0/125 (0.00%)
Hyperthermia † 1	0/128 (0.00%)	1/120 (0.83%)	0/125 (0.00%)
Impaired healing † 1	0/128 (0.00%)	0/120 (0.00%)	1/125 (0.80%)
Mucosal inflammation † 1	1/128 (0.78%)	0/120 (0.00%)	0/125 (0.00%)
Hepatobiliary disorders
Cholelithiasis † 1	1/128 (0.78%)	0/120 (0.00%)	0/125 (0.00%)
Hepatic vein thrombosis † 1	1/128 (0.78%)	0/120 (0.00%)	0/125 (0.00%)
Hepatotoxicity † 1	1/128 (0.78%)	0/120 (0.00%)	0/125 (0.00%)
Portal vein thrombosis † 1	0/128 (0.00%)	0/120 (0.00%)	1/125 (0.80%)
Infections and infestations
Pneumonia † 1	3/128 (2.34%)	1/120 (0.83%)	7/125 (5.60%)
Anal abscess † 1	1/128 (0.78%)	0/120 (0.00%)	1/125 (0.80%)
Bronchitis † 1	1/128 (0.78%)	0/120 (0.00%)	1/125 (0.80%)
Device related infection † 1	0/128 (0.00%)	1/120 (0.83%)	1/125 (0.80%)
Sepsis † 1	2/128 (1.56%)	0/120 (0.00%)	0/125 (0.00%)
Abscess limb † 1	1/128 (0.78%)	0/120 (0.00%)	0/125 (0.00%)
Clostridial infection † 1	1/128 (0.78%)	0/120 (0.00%)	0/125 (0.00%)
Diverticulitis † 1	0/128 (0.00%)	0/120 (0.00%)	1/125 (0.80%)
Gastroenteritis norovirus † 1	0/128 (0.00%)	0/120 (0.00%)	1/125 (0.80%)
Intervertebral discitis † 1	0/128 (0.00%)	1/120 (0.83%)	0/125 (0.00%)
Lung infection † 1	0/128 (0.00%)	0/120 (0.00%)	1/125 (0.80%)
Oesophageal candidiasis † 1	1/128 (0.78%)	0/120 (0.00%)	0/125 (0.00%)
Post procedural infection † 1	1/128 (0.78%)	0/120 (0.00%)	0/125 (0.00%)
Pulmonary sepsis † 1	0/128 (0.00%)	0/120 (0.00%)	1/125 (0.80%)
Scrub typhus † 1	0/128 (0.00%)	0/120 (0.00%)	1/125 (0.80%)
Septic shock † 1	1/128 (0.78%)	0/120 (0.00%)	0/125 (0.00%)
Sinusitis † 1	1/128 (0.78%)	0/120 (0.00%)	0/125 (0.00%)
Upper respiratory tract infection † 1	0/128 (0.00%)	0/120 (0.00%)	1/125 (0.80%)
Urinary tract infection † 1	0/128 (0.00%)	0/120 (0.00%)	1/125 (0.80%)
Injury, poisoning and procedural complications
Femoral neck fracture † 1	1/128 (0.78%)	0/120 (0.00%)	0/125 (0.00%)
Respiratory fume inhalation disorder † 1	0/128 (0.00%)	1/120 (0.83%)	0/125 (0.00%)
Investigations
General physical condition abnormal † 1	2/128 (1.56%)	0/120 (0.00%)	1/125 (0.80%)
Gamma-glutamyltransferase increased † 1	0/128 (0.00%)	1/120 (0.83%)	0/125 (0.00%)
White blood cell count decreased † 1	1/128 (0.78%)	0/120 (0.00%)	0/125 (0.00%)
Metabolism and nutrition disorders
Dehydration † 1	3/128 (2.34%)	0/120 (0.00%)	1/125 (0.80%)
Decreased appetite † 1	3/128 (2.34%)	0/120 (0.00%)	0/125 (0.00%)
Hyperglycaemia † 1	0/128 (0.00%)	0/120 (0.00%)	2/125 (1.60%)
Hypokalaemia † 1	0/128 (0.00%)	0/120 (0.00%)	2/125 (1.60%)
Hyponatraemia † 1	1/128 (0.78%)	0/120 (0.00%)	1/125 (0.80%)
Hypercalcaemia † 1	0/128 (0.00%)	0/120 (0.00%)	1/125 (0.80%)
Hypercreatininaemia † 1	0/128 (0.00%)	1/120 (0.83%)	0/125 (0.00%)
Hypocalcaemia † 1	0/128 (0.00%)	0/120 (0.00%)	1/125 (0.80%)
Musculoskeletal and connective tissue disorders
Back pain † 1	1/128 (0.78%)	0/120 (0.00%)	1/125 (0.80%)
Muscle spasms † 1	1/128 (0.78%)	0/120 (0.00%)	0/125 (0.00%)
Musculoskeletal pain † 1	0/128 (0.00%)	1/120 (0.83%)	0/125 (0.00%)
Pain in extremity † 1	0/128 (0.00%)	1/120 (0.83%)	0/125 (0.00%)
Nervous system disorders
Transient ischaemic attack † 1	0/128 (0.00%)	0/120 (0.00%)	2/125 (1.60%)
Cerebral haemorrhage † 1	1/128 (0.78%)	0/120 (0.00%)	0/125 (0.00%)
Dizziness † 1	0/128 (0.00%)	0/120 (0.00%)	1/125 (0.80%)
Headache † 1	0/128 (0.00%)	0/120 (0.00%)	1/125 (0.80%)
Nervous system disorder † 1	0/128 (0.00%)	0/120 (0.00%)	1/125 (0.80%)
Posterior reversible encephalopathy syndrome † 1	1/128 (0.78%)	0/120 (0.00%)	0/125 (0.00%)
Presyncope † 1	1/128 (0.78%)	0/120 (0.00%)	0/125 (0.00%)
Viith nerve paralysis † 1	1/128 (0.78%)	0/120 (0.00%)	0/125 (0.00%)
Psychiatric disorders
Confusional state † 1	1/128 (0.78%)	0/120 (0.00%)	0/125 (0.00%)
Psychotic disorder † 1	0/128 (0.00%)	0/120 (0.00%)	1/125 (0.80%)
Renal and urinary disorders
Renal failure † 1	4/128 (3.13%)	0/120 (0.00%)	2/125 (1.60%)
Renal failure acute † 1	2/128 (1.56%)	0/120 (0.00%)	0/125 (0.00%)
Renal impairment † 1	1/128 (0.78%)	0/120 (0.00%)	0/125 (0.00%)
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism † 1	9/128 (7.03%)	3/120 (2.50%)	2/125 (1.60%)
Dyspnoea † 1	3/128 (2.34%)	1/120 (0.83%)	1/125 (0.80%)
Haemoptysis † 1	2/128 (1.56%)	2/120 (1.67%)	0/125 (0.00%)
Pneumothorax † 1	2/128 (1.56%)	0/120 (0.00%)	1/125 (0.80%)
Acute respiratory failure † 1	0/128 (0.00%)	1/120 (0.83%)	0/125 (0.00%)
Bronchopleural fistula † 1	1/128 (0.78%)	0/120 (0.00%)	0/125 (0.00%)
Pleural effusion † 1	1/128 (0.78%)	0/120 (0.00%)	0/125 (0.00%)
Respiratory failure † 1	1/128 (0.78%)	0/120 (0.00%)	0/125 (0.00%)
Skin and subcutaneous tissue disorders
Dermal cyst † 1	1/128 (0.78%)	0/120 (0.00%)	0/125 (0.00%)
Vascular disorders
Deep vein thrombosis † 1	0/128 (0.00%)	2/120 (1.67%)	0/125 (0.00%)
Thrombophlebitis † 1	1/128 (0.78%)	0/120 (0.00%)	1/125 (0.80%)
Embolism arterial † 1	1/128 (0.78%)	0/120 (0.00%)	0/125 (0.00%)
Embolism venous † 1	0/128 (0.00%)	0/120 (0.00%)	1/125 (0.80%)
Hypertension † 1	0/128 (0.00%)	1/120 (0.83%)	0/125 (0.00%)
Iliac artery embolism † 1	1/128 (0.78%)	0/120 (0.00%)	0/125 (0.00%)
Ischaemia † 1	1/128 (0.78%)	0/120 (0.00%)	0/125 (0.00%)
Peripheral arterial occlusive disease † 1	1/128 (0.78%)	0/120 (0.00%)	0/125 (0.00%)
Peripheral ischaemia † 1	0/128 (0.00%)	0/120 (0.00%)	1/125 (0.80%)
Thrombophlebitis superficial † 1	0/128 (0.00%)	0/120 (0.00%)	1/125 (0.80%)
Vasculitis necrotising † 1	1/128 (0.78%)	0/120 (0.00%)	0/125 (0.00%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 14.0
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	No Maintenance Treatment	Maintenance Treatment Arm A	Maintenance Treatment Arm B
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	105/128 (82.03%)	115/120 (95.83%)	120/125 (96.00%)
Blood and lymphatic system disorders
Neutropenia † 1	5/128 (3.91%)	26/120 (21.67%)	26/125 (20.80%)
Anaemia † 1	17/128 (13.28%)	20/120 (16.67%)	21/125 (16.80%)
Thrombocytopenia † 1	4/128 (3.13%)	8/120 (6.67%)	3/125 (2.40%)
Leukopenia † 1	2/128 (1.56%)	6/120 (5.00%)	8/125 (6.40%)
Cardiac disorders
Tachycardia † 1	4/128 (3.13%)	6/120 (5.00%)	9/125 (7.20%)
Eye disorders
Lacrimation increased † 1	4/128 (3.13%)	3/120 (2.50%)	16/125 (12.80%)
Conjunctivitis † 1	0/128 (0.00%)	6/120 (5.00%)	5/125 (4.00%)
Gastrointestinal disorders
Nausea † 1	47/128 (36.72%)	73/120 (60.83%)	77/125 (61.60%)
Vomiting † 1	21/128 (16.41%)	28/120 (23.33%)	33/125 (26.40%)
Constipation † 1	21/128 (16.41%)	33/120 (27.50%)	32/125 (25.60%)
Diarrhoea † 1	22/128 (17.19%)	16/120 (13.33%)	35/125 (28.00%)
Abdominal pain upper † 1	8/128 (6.25%)	8/120 (6.67%)	11/125 (8.80%)
Abdominal pain † 1	4/128 (3.13%)	5/120 (4.17%)	8/125 (6.40%)
Stomatitis † 1	3/128 (2.34%)	6/120 (5.00%)	8/125 (6.40%)
Dry mouth † 1	2/128 (1.56%)	1/120 (0.83%)	7/125 (5.60%)
General disorders
Asthenia † 1	25/128 (19.53%)	42/120 (35.00%)	31/125 (24.80%)
Fatigue † 1	22/128 (17.19%)	22/120 (18.33%)	40/125 (32.00%)
Chest pain † 1	11/128 (8.59%)	15/120 (12.50%)	15/125 (12.00%)
Mucosal inflammation † 1	12/128 (9.38%)	7/120 (5.83%)	15/125 (12.00%)
Oedema peripheral † 1	7/128 (5.47%)	4/120 (3.33%)	19/125 (15.20%)
Pyrexia † 1	8/128 (6.25%)	6/120 (5.00%)	16/125 (12.80%)
Infections and infestations
Nasopharyngitis † 1	1/128 (0.78%)	8/120 (6.67%)	19/125 (15.20%)
Bronchitis † 1	1/128 (0.78%)	8/120 (6.67%)	7/125 (5.60%)
Urinary tract infection † 1	5/128 (3.91%)	3/120 (2.50%)	7/125 (5.60%)
Investigations
Weight decreased † 1	16/128 (12.50%)	7/120 (5.83%)	8/125 (6.40%)
Blood creatinine increased † 1	1/128 (0.78%)	6/120 (5.00%)	11/125 (8.80%)
Haemoglobin decreased † 1	7/128 (5.47%)	0/120 (0.00%)	7/125 (5.60%)
Alanine aminotransferase increased † 1	0/128 (0.00%)	3/120 (2.50%)	7/125 (5.60%)
Metabolism and nutrition disorders
Decreased appetite † 1	24/128 (18.75%)	23/120 (19.17%)	32/125 (25.60%)
Hyperglycaemia † 1	7/128 (5.47%)	2/120 (1.67%)	8/125 (6.40%)
Musculoskeletal and connective tissue disorders
Back pain † 1	12/128 (9.38%)	11/120 (9.17%)	13/125 (10.40%)
Musculoskeletal pain † 1	1/128 (0.78%)	14/120 (11.67%)	11/125 (8.80%)
Arthralgia † 1	4/128 (3.13%)	11/120 (9.17%)	11/125 (8.80%)
Pain in extremity † 1	3/128 (2.34%)	5/120 (4.17%)	11/125 (8.80%)
Bone pain † 1	1/128 (0.78%)	11/120 (9.17%)	2/125 (1.60%)
Nervous system disorders
Headache † 1	10/128 (7.81%)	19/120 (15.83%)	26/125 (20.80%)
Dizziness † 1	9/128 (7.03%)	7/120 (5.83%)	11/125 (8.80%)
Paraesthesia † 1	3/128 (2.34%)	4/120 (3.33%)	11/125 (8.80%)
Dysgeusia † 1	7/128 (5.47%)	6/120 (5.00%)	7/125 (5.60%)
Peripheral sensory neuropathy † 1	2/128 (1.56%)	3/120 (2.50%)	9/125 (7.20%)
Psychiatric disorders
Insomnia † 1	4/128 (3.13%)	9/120 (7.50%)	9/125 (7.20%)
Renal and urinary disorders
Proteinuria † 1	4/128 (3.13%)	8/120 (6.67%)	10/125 (8.00%)
Renal impairment † 1	3/128 (2.34%)	6/120 (5.00%)	7/125 (5.60%)
Respiratory, thoracic and mediastinal disorders
Cough † 1	19/128 (14.84%)	27/120 (22.50%)	27/125 (21.60%)
Epistaxis † 1	17/128 (13.28%)	26/120 (21.67%)	24/125 (19.20%)
Dyspnoea † 1	12/128 (9.38%)	21/120 (17.50%)	26/125 (20.80%)
Dysphonia † 1	5/128 (3.91%)	7/120 (5.83%)	8/125 (6.40%)
Dyspnoea exertional † 1	1/128 (0.78%)	6/120 (5.00%)	4/125 (3.20%)
Rhinorrhoea † 1	1/128 (0.78%)	3/120 (2.50%)	9/125 (7.20%)
Skin and subcutaneous tissue disorders
Alopecia † 1	8/128 (6.25%)	11/120 (9.17%)	20/125 (16.00%)
Rash † 1	0/128 (0.00%)	6/120 (5.00%)	7/125 (5.60%)
Vascular disorders
Hypertension † 1	23/128 (17.97%)	43/120 (35.83%)	55/125 (44.00%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 14.0

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):

Barlesi F, Scherpereel A, Rittmeyer A, Pazzola A, Ferrer Tur N, Kim JH, Ahn MJ, Aerts JG, Gorbunova V, Vikstrom A, Wong EK, Perez-Moreno P, Mitchell L, Groen HJ. Randomized phase III trial of maintenance bevacizumab with or without pemetrexed after first-line induction with bevacizumab, cisplatin, and pemetrexed in advanced nonsquamous non-small-cell lung cancer: AVAPERL (MO22089). J Clin Oncol. 2013 Aug 20;31(24):3004-11. doi: 10.1200/JCO.2012.42.3749. Epub 2013 Jul 8.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT00961415
• Other Study ID Numbers: MO22089; 2008-007008-27
• First Submitted: August 18, 2009
• First Posted: August 19, 2009
• Results First Submitted: November 30, 2015
• Results First Posted: February 22, 2016
• Last Update Posted: February 22, 2016