Trial Outcomes & Findings for A Study of Bevacizumab in Combination With Standard of Care Treatment in Participants With Advanced Non-squamous Non-small Cell Lung Cancer (NSCLC) (NCT NCT01351415)

Last Updated: 2017-09-18

Results Overview

Overall survival (OS) was defined as the time from the date of randomization at first progression of disease to the date of death, regardless of the cause of death.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

485 participants

Primary outcome timeframe

Up to data cut-off date 24 June 2016 (approximately 5 years)

Results posted on

2017-09-18

Participant Flow

This phase 3b study was conducted across 16 different countries and enrolled 485 participants. Participants were 18 years or older and had locally recurrent or metastatic non-squamous Non-Small Cell Lung Cancer (NSCLC)

A total of 485 participants were enrolled and randomized into the study. Of these, 475 participants were treated; 243 participants received bevacizumab plus standard of care (SoC) and 232 participants received SoC alone. The study was terminated 60 months after study start, as per protocol, but was not ended prematurely.

Participant milestones

Participant milestones
Measure	Bevacizumab + Standard of Care Participants received bevacizumab on Day 1 of every 21-days cycle along with standard of care, until the occurrence of an unacceptable toxicity or withdrawal of consent (whichever occurs first).	Standard of Care Participants received investigator's choice of standard of care (Erlotinib or Docetaxel or Pemetrexed) according to local practice until the occurrence of an unacceptable toxicity or withdrawal of consent (whichever occurs first).
Overall Study STARTED	245	240
Overall Study Treated Participants	243	232
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	245	240

Reasons for withdrawal

Reasons for withdrawal
Measure	Bevacizumab + Standard of Care Participants received bevacizumab on Day 1 of every 21-days cycle along with standard of care, until the occurrence of an unacceptable toxicity or withdrawal of consent (whichever occurs first).	Standard of Care Participants received investigator's choice of standard of care (Erlotinib or Docetaxel or Pemetrexed) according to local practice until the occurrence of an unacceptable toxicity or withdrawal of consent (whichever occurs first).
Overall Study Withdrawal by Subject	15	17
Overall Study Trial termination by the Sponsor	28	19
Overall Study Lost to Follow-up	5	7
Overall Study Death	190	187
Overall Study Physician Decision	2	3
Overall Study Reason unknown	0	2
Overall Study Never Started	5	5

Baseline Characteristics

A Study of Bevacizumab in Combination With Standard of Care Treatment in Participants With Advanced Non-squamous Non-small Cell Lung Cancer (NSCLC)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Bevacizumab + Standard of Care n=245 Participants Participants received bevacizumab on Day 1 of every 21-days cycle along with standard of care, until the occurrence of an unacceptable toxicity or withdrawal of consent (whichever occurs first).	Standard of Care n=240 Participants Participants received investigator's choice of standard of care (Erlotinib or Docetaxel or Pemetrexed) according to local practice until the occurrence of an unacceptable toxicity or withdrawal of consent (whichever occurs first).	Total n=485 Participants Total of all reporting groups
Age, Continuous	61.5 Years STANDARD_DEVIATION 9.61 • n=5 Participants	61.8 Years STANDARD_DEVIATION 9.29 • n=7 Participants	61.6 Years STANDARD_DEVIATION 9.44 • n=5 Participants
Sex: Female, Male Female	90 Participants n=5 Participants	102 Participants n=7 Participants	192 Participants n=5 Participants
Sex: Female, Male Male	155 Participants n=5 Participants	138 Participants n=7 Participants	293 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to data cut-off date 24 June 2016 (approximately 5 years)

Population: Intent to treat population included all randomized participants.

Overall survival (OS) was defined as the time from the date of randomization at first progression of disease to the date of death, regardless of the cause of death.

Outcome measures

Outcome measures
Measure	Bevacizumab + Standard of Care n=245 Participants Participants received bevacizumab on Day 1 of every 21-days cycle along with standard of care, until the occurrence of an unacceptable toxicity or withdrawal of consent (whichever occurs first).	Standard of Care n=240 Participants Participants received investigator's choice of standard of care (Erlotinib or Docetaxel or Pemetrexed) according to local practice until the occurrence of an unacceptable toxicity or withdrawal of consent (whichever occurs first).
Overall Survival (OS)	11.86 Months Interval 10.22 to 13.67	10.22 Months Interval 8.61 to 11.93

SECONDARY outcome

Timeframe: Up to data cut-off date 24 June 2016 (approximately 5 years)

Population: Intent to treat population included all randomized participants.

PFS was defined as the time from start of treatment to the first event of death or PD. Tumor response was assessed by the IRF according to RECIST v1.1. Disease progression or PD was defined as ≥20% increase in sum LD in reference to the smallest on-study sum LD, or the appearance of new lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. PFS2 is defined as the time between randomization at PD1 and the date of PD2 or death, whichever occurs first. PFS3 is defined as the time between PD2 and the date of PD3 or death, whichever occurs first.

Outcome measures

Outcome measures
Measure	Bevacizumab + Standard of Care n=245 Participants Participants received bevacizumab on Day 1 of every 21-days cycle along with standard of care, until the occurrence of an unacceptable toxicity or withdrawal of consent (whichever occurs first).	Standard of Care n=240 Participants Participants received investigator's choice of standard of care (Erlotinib or Docetaxel or Pemetrexed) according to local practice until the occurrence of an unacceptable toxicity or withdrawal of consent (whichever occurs first).
Progression-free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) PFS 2	5.45 Months Interval 4.21 to 5.68	3.98 Months Interval 3.38 to 4.3
Progression-free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) PFS 3	4.01 Months Interval 2.86 to 4.47	2.60 Months Interval 2.33 to 2.92

SECONDARY outcome

Timeframe: Up to data cut-off date 24 June 2016 (approximately 5 years)

Population: Intent to treat population included all randomized participants.

The objective response is defined as complete response (CR) or partial response (PR) assessed according to the RECIST v.1.1 criteria with baseline tumour assessment as the reference. CR was defined as disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker levels. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR was defined as greater than or equal to (≥) 30 percent (%) decrease in sum of longest diameter (LD) of target lesions in reference to Baseline sum LD. Response was to be confirmed ≥4 weeks after the initial assessment of CR or PR.

Outcome measures

Outcome measures
Measure	Bevacizumab + Standard of Care n=245 Participants Participants received bevacizumab on Day 1 of every 21-days cycle along with standard of care, until the occurrence of an unacceptable toxicity or withdrawal of consent (whichever occurs first).	Standard of Care n=240 Participants Participants received investigator's choice of standard of care (Erlotinib or Docetaxel or Pemetrexed) according to local practice until the occurrence of an unacceptable toxicity or withdrawal of consent (whichever occurs first).
Percentage of Participants With Objective Response According to RECIST v1.1	8.6 Percentage of Participants Interval 5.86 to 12.21	6.3 Percentage of Participants Interval 3.91 to 9.5

SECONDARY outcome

Timeframe: Up to data cut-off date 24 June 2016 (approximately 5 years)

Population: Intent to treat population included all randomized participants.

The disease control rate is defined as CR or PR or stable disease (SD) assessed according to the RECIST v.1.1 criteria with baseline tumour assessment as the reference. SD was defined as neither sufficient shrinkage to qualify for a PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of the longest diameter since treatment started for target lesions and the persistence of 1 or more non-target lesions.

Outcome measures

Outcome measures
Measure	Bevacizumab + Standard of Care n=245 Participants Participants received bevacizumab on Day 1 of every 21-days cycle along with standard of care, until the occurrence of an unacceptable toxicity or withdrawal of consent (whichever occurs first).	Standard of Care n=240 Participants Participants received investigator's choice of standard of care (Erlotinib or Docetaxel or Pemetrexed) according to local practice until the occurrence of an unacceptable toxicity or withdrawal of consent (whichever occurs first).
Percentage of Participants With Disease Control According to RECIST v1.1	80.2 Percentage of Participants Interval 75.57 to 84.36	77.0 Percentage of Participants Interval 72.06 to 81.41

SECONDARY outcome

Timeframe: Up to data cut-off date 24 June 2016 (approximately 5 years)

Population: Intent to treat population included all randomized participants.

Duration of response is defined as the time that measurement criteria are met for objective response (CR/PR) (whichever status is recorded first) until the first date of progression or death is documented. CR was defined as disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker levels. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than \< 10 mm. PR was defined as greater than or equal to ≥30 % decrease in sum of longest diameter of target lesions in reference to baseline sum longest diameter.

Outcome measures

Outcome measures
Measure	Bevacizumab + Standard of Care n=245 Participants Participants received bevacizumab on Day 1 of every 21-days cycle along with standard of care, until the occurrence of an unacceptable toxicity or withdrawal of consent (whichever occurs first).	Standard of Care n=240 Participants Participants received investigator's choice of standard of care (Erlotinib or Docetaxel or Pemetrexed) according to local practice until the occurrence of an unacceptable toxicity or withdrawal of consent (whichever occurs first).
Duration of Response (DoR) According to RECIST v1.1	7.46 Months Interval 5.39 to 8.54	6.24 Months Interval 3.52 to 6.83

SECONDARY outcome

Timeframe: Up to data cut-off date 24 June 2016 (approximately 5 years)

Population: The safety population included all participants who had received at least one dose of any study drug.

An AE was considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. Preexisting conditions that worsened during the study and laboratory or clinical tests that resulted in a change in treatment or discontinuation from study drug were reported as adverse events. A SAE was any experience that: resulted in death, was life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect or was medically significant.

Outcome measures

Outcome measures
Measure	Bevacizumab + Standard of Care n=243 Participants Participants received bevacizumab on Day 1 of every 21-days cycle along with standard of care, until the occurrence of an unacceptable toxicity or withdrawal of consent (whichever occurs first).	Standard of Care n=232 Participants Participants received investigator's choice of standard of care (Erlotinib or Docetaxel or Pemetrexed) according to local practice until the occurrence of an unacceptable toxicity or withdrawal of consent (whichever occurs first).
Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) AEs	97.5 Percentage of Participants	96.1 Percentage of Participants
Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) SAEs	51.9 Percentage of Participants	37.1 Percentage of Participants

SECONDARY outcome

Timeframe: Up to data cut-off date 24 June 2016 (approximately 5 years)

Population: Intent to treat population included all randomized participants.

The time to progression was defined as the time from baseline until disease progression as determined by the RECIST v1.1. TTP2 is defined as the interval between the day of randomization at PD1 and PD2. TTP3 is defined as the interval between the day of PD2 and PD3. PD was defined as ≥20% increase in sum LD in reference to the smallest on-study sum LD, or the appearance of new lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.

Outcome measures

Outcome measures
Measure	Bevacizumab + Standard of Care n=245 Participants Participants received bevacizumab on Day 1 of every 21-days cycle along with standard of care, until the occurrence of an unacceptable toxicity or withdrawal of consent (whichever occurs first).	Standard of Care n=240 Participants Participants received investigator's choice of standard of care (Erlotinib or Docetaxel or Pemetrexed) according to local practice until the occurrence of an unacceptable toxicity or withdrawal of consent (whichever occurs first).
Time to Progression (TTP) According to RECIST v1.1 TTP2	5.55 Months Interval 4.86 to 6.18	4.21 Months Interval 3.75 to 5.06
Time to Progression (TTP) According to RECIST v1.1 TTP3	4.07 Months Interval 3.25 to 4.63	2.73 Months Interval 2.37 to 3.06

SECONDARY outcome

Timeframe: Month 6, 12, 18

Population: Intent to treat population included all randomized participants.

Percentage of participants who were alive at Month 6, 12 and 18 were reported.

Outcome measures

Outcome measures
Measure	Bevacizumab + Standard of Care n=245 Participants Participants received bevacizumab on Day 1 of every 21-days cycle along with standard of care, until the occurrence of an unacceptable toxicity or withdrawal of consent (whichever occurs first).	Standard of Care n=240 Participants Participants received investigator's choice of standard of care (Erlotinib or Docetaxel or Pemetrexed) according to local practice until the occurrence of an unacceptable toxicity or withdrawal of consent (whichever occurs first).
Percentage of Participants Who Are Alive at Month 6, 12, and 18 Month 18	0.4 Percentage of Participants Interval 0.31 to 0.41	0.3 Percentage of Participants Interval 0.25 to 0.36
Percentage of Participants Who Are Alive at Month 6, 12, and 18 Month 6	0.8 Percentage of Participants Interval 0.73 to 0.82	0.7 Percentage of Participants Interval 0.62 to 0.72
Percentage of Participants Who Are Alive at Month 6, 12, and 18 Month 12	0.5 Percentage of Participants Interval 0.44 to 0.54	0.4 Percentage of Participants Interval 0.39 to 0.5

Adverse Events

Bevacizumab + Standard of Care

Serious events: 126 serious events

Other events: 226 other events

Deaths: 0 deaths

Standard of Care

Serious events: 86 serious events

Other events: 215 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: 888-6821-8590

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