Non-Squamous Non-Small Cell Lung Cancer
Conditions
Brief summary
This single arm study will assess the safety and efficacy of Avastin combined with platinum-containing chemotherapy regimens in patients with advanced or recurrent non-squamous non-small cell lung cancer (NSCLC). Avastin will be given as first-line treatment in combination with platinum-based chemotherapy or in combination with any standard of care NSCLC first-line chemotherapy used in line with the licensed national prescribing information. Eligible patients will receive Avastin (15mg/kg iv on day 1 of each 3 week cycle) concomitantly with chemotherapy. Avastin treatment will continue after completion of chemotherapy cycles until disease progression, and the target sample size is 500+ individuals.
Interventions
As prescribed
DRUGBevacizumab [Avastin]
15 mg/kg IV on Day 1 of each 3 week cycle
Sponsors
Hoffmann-La Roche
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* adult patients, \>=18 years of age; * histologically or cytologically documented inoperable, locally advanced ( stage III), metastatic (stage IV) or recurrent NSCLC other than squamous cell (tumors of mixed histology should be categorized by the predominant cell type); * ECOG PS status 0-2; * life expectancy \>= 12weeks; * adequate renal, liver and hematological function.
Exclusion criteria
* mixed, non-small and small cell tumors, or mixed adenosquamous carcinomas with a predominant squamous component; * hemoptysis (\>=1/2 teaspoon of bright red blood) in previous 3 months; * evidence of tumor invading major blood vessels on imaging; * evidence of CNS metastases, even if previously treated. * major surgery (including open biopsy), significant traumatic injury within 28 days prior to enrolment, or anticipation of need for major surgery during study treatment; * prior chemotherapy for stage IIIb/IV disease.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events of Special Interest | Up to 3 years | Participants with adverse events (AEs) of special interest (hypertension, proteinuria, wound healing complications, gastrointestinal perforation, arterial and venous thromboembolic events, hemoptysis, Central Nervous System (CNS) bleeding, other hemorrhage events and congestive heart failure) were reported. |
| Number of Participants With Serious Adverse Events Related to Bevacizumab | Up to 3 years | Participants with serious adverse events (SAEs) related to bevacizumab were reported for the duration of the study. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Overall Survival | Up to 3 years | Overall survival time was defined as time between first bevacizumab administration and date of death, irrespective of the cause of death. Participants for whom no death was captured on the clinical database were censored at the most recent date they were known to be alive. |
| Time to Disease Progression | Up to 3 years | Time to disease progression was defined as time between first bevacizumab administration and date of first occurrence of progressive disease. Participants who had not progressed at the time of study completion (including participants who died before progressive disease) or who were lost to follow-up were censored at the last bevacizumab administration date. Progressive disease is defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Time to disease progression was assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0. |
| Number of Participants With Central Nervous System Bleeding | Up to 3 years | The incidence of central nervous system (CNS) bleeding was reported for participants who developed CNS metastases during the study period and who did not have Computed Tomography (CT) or magnetic resonance imaging (MRI) techniques of the head performed at baseline. |
Countries
Argentina, Australia, Austria, Bosnia and Herzegovina, Brazil, Canada, China, Colombia, Czechia, Denmark, Ecuador, Egypt, Estonia, Finland, France, Germany, Hong Kong, Hungary, Iceland, Israel, Italy, Latvia, Lebanon, Lithuania, Mexico, Netherlands, Poland, Portugal, Romania, Russia, Serbia, Slovakia, Slovenia, Spain, Sweden, Switzerland, Taiwan, Turkey (Türkiye), United Kingdom, Venezuela
Participant flow
Recruitment details
This study was conducted at 384 sites in 39 countries from 21 August 2006 to 30 June 2009.
Pre-assignment details
A total of 2252 participants were enrolled into the study, of which 2172 received the study drug. A total of 80 randomized participants did not receive study drug.
Participants by arm
| Arm | Count |
|---|---|
| Bevacizumab + Chemotherapy Eligible participants with advanced or recurrent non-squamous non-small cell lung cancer (NSCLC) were administered bevacizumab infusions at a dose of 7.5 milligram per kilogram (mg/kg) or 15 mg/kg (investigator's choice) on Day 1 and then every 3 weeks, intravenously (IV) for a maximum of 6 cycles in combination with the standard of care NSCLC first-line chemotherapy in line with the licensed national prescribing information, during the treatment period. The initial dose of bevacizumab was to be administered following chemotherapy; all subsequent doses could be given before or after chemotherapy. After the end of chemotherapy participants without disease progression could continue bevacizumab as maintenance therapy until confirmed disease progression, unacceptable toxicity or participant consent withdrawal. Participants were followed-up through a final-visit (28 days after last bevacizumab infusion) and then every 3 months until death. | 2,172 |
| Total | 2,172 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 515 |
| Overall Study | Did not complete final visit | 4 |
| Overall Study | Lost to Follow-up | 31 |
| Overall Study | Other Reasons | 121 |
| Overall Study | Progressive disease | 1,328 |
| Overall Study | Protocol Violation | 21 |
| Overall Study | Termination of the study | 108 |
| Overall Study | Withdrawal by Subject | 111 |
Baseline characteristics
| Characteristic | Bevacizumab + Chemotherapy |
|---|---|
| Age, Continuous | 58.8 years STANDARD_DEVIATION 10.3 |
| Sex: Female, Male Female | 866 Participants |
| Sex: Female, Male Male | 1306 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 1,982 / 2,212 |
| serious Total, serious adverse events | 834 / 2,212 |
Outcome results
Primary
Number of Participants With Adverse Events of Special Interest
Participants with adverse events (AEs) of special interest (hypertension, proteinuria, wound healing complications, gastrointestinal perforation, arterial and venous thromboembolic events, hemoptysis, Central Nervous System (CNS) bleeding, other hemorrhage events and congestive heart failure) were reported.
Time frame: Up to 3 years
Population: The ITT population included all participants with at least one valid post-baseline (Day -28 to -1) assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bevacizumab + Chemotherapy | Number of Participants With Adverse Events of Special Interest | Hypertension | 687 participants |
| Bevacizumab + Chemotherapy | Number of Participants With Adverse Events of Special Interest | Proteinuria | 672 participants |
| Bevacizumab + Chemotherapy | Number of Participants With Adverse Events of Special Interest | CNS bleeding | 7 participants |
| Bevacizumab + Chemotherapy | Number of Participants With Adverse Events of Special Interest | Wound healing complication | 26 participants |
| Bevacizumab + Chemotherapy | Number of Participants With Adverse Events of Special Interest | Gastrointestinal perforation | 30 participants |
| Bevacizumab + Chemotherapy | Number of Participants With Adverse Events of Special Interest | Arterial/Venous thromboembolic events | 274 participants |
| Bevacizumab + Chemotherapy | Number of Participants With Adverse Events of Special Interest | Hemoptysis | 176 participants |
| Bevacizumab + Chemotherapy | Number of Participants With Adverse Events of Special Interest | Other hemorrhage events | 744 participants |
| Bevacizumab + Chemotherapy | Number of Participants With Adverse Events of Special Interest | Congestive heart failure | 17 participants |
Primary
Number of Participants With Serious Adverse Events Related to Bevacizumab
Participants with serious adverse events (SAEs) related to bevacizumab were reported for the duration of the study.
Time frame: Up to 3 years
Population: The ITT population included all participants with at least one valid post-baseline (Day -28 to -1) assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bevacizumab + Chemotherapy | Number of Participants With Serious Adverse Events Related to Bevacizumab | 283 participants |
Secondary
Duration of Overall Survival
Overall survival time was defined as time between first bevacizumab administration and date of death, irrespective of the cause of death. Participants for whom no death was captured on the clinical database were censored at the most recent date they were known to be alive.
Time frame: Up to 3 years
Population: The ITT population included all participants with at least one valid post-baseline (Day -28 to -1) assessment. Participants available at the time of assessment were included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bevacizumab + Chemotherapy | Duration of Overall Survival | 14.6 Months |
Secondary
Number of Participants With Central Nervous System Bleeding
The incidence of central nervous system (CNS) bleeding was reported for participants who developed CNS metastases during the study period and who did not have Computed Tomography (CT) or magnetic resonance imaging (MRI) techniques of the head performed at baseline.
Time frame: Up to 3 years
Population: The ITT population was used for analysis, which included all participants with at least one valid post-baseline (Day -28 to -1) assessment. n = number of participants available at the time of assessment who were included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bevacizumab + Chemotherapy | Number of Participants With Central Nervous System Bleeding | With CNS metastases (n = 281) | 12 participants |
| Bevacizumab + Chemotherapy | Number of Participants With Central Nervous System Bleeding | Without CT/MRI scans (n = 367) | 16 participants |
Secondary
Time to Disease Progression
Time to disease progression was defined as time between first bevacizumab administration and date of first occurrence of progressive disease. Participants who had not progressed at the time of study completion (including participants who died before progressive disease) or who were lost to follow-up were censored at the last bevacizumab administration date. Progressive disease is defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Time to disease progression was assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0.
Time frame: Up to 3 years
Population: The ITT population was considered for analysis, which included all participants with at least one valid post-baseline (Day -28 to -1) assessment. Participants available at the time of assessment were included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bevacizumab + Chemotherapy | Time to Disease Progression | 7.8 Months |