Non-Small Cell Lung Cancer
Conditions
Keywords
NSCLC, Lung Cancer, ATLAS, Avastin, Tarceva
Brief summary
This is a Phase IIIb, multicenter, randomized, placebo-controlled trial to evaluate the safety and efficacy of chemotherapy+bevacizumab followed by bevacizumab+erlotinib versus bevacizumab+erlotinib placebo in subjects with locally advanced or metastatic NSCLC.
Interventions
DRUGbevacizumab
Intravenous repeating dose
DRUGplacebo
Oral repeating dose
DRUGerlotinib HCl
Oral repeating dose
Sponsors
Genentech, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Signed Informed Consent Form * Histologically or cytologically confirmed NSCLC * Advanced NSCLC or recurrent disease * INR no greater than 1.3 and aPTT no greater than upper limits of normal (ULN) within 28 days prior to enrollment for subjects not on low molecular weight heparin or fondaparinux. Subjects on low molecular weight heparin or fondaparinux are not required to meet INR or aPTT limits. Chronic full-dose anticoagulation with warfarin is not permitted. * 18 years of age or older * For women of childbearing potential and sexually active men, use of an accepted and effective method of contraception (hormonal or barrier methods, abstinence) prior to enrollment and for the duration of the study
Exclusion criteria
* Prior systemic chemotherapy in the metastatic setting * Treatment with an investigational or marketed agent that acts by either EGFR inhibition or anti-angiogenesis mechanisms * Pregnancy or lactation * Any other medical condition, including mental illness or substance abuse, deemed by the clinician to be likely to interfere with a subject's ability to provide informed consent, cooperate, and participate in the study, or to interfere with the interpretation of the results * Active infection or a fever within 3 days of enrollment * Active malignancy other than lung cancer * Radiation therapy to sites other than whole brain within 14 days prior to enrollment * History of gross hemoptysis within 3 months prior to enrollment * Known hypersensitivity to any of the components of cytotoxic chemotherapy combinations, bevacizumab, or tyrosine kinase inhibitors * Inadequately controlled hypertension * Unstable angina or New York Heart Association Grade II or greater CHF * Abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to enrollment * History of myocardial infarction within 6 months prior to enrollment * History of stroke within 6 months prior to enrollment * Symptomatic peripheral vascular disease within 6 months prior to enrollment * Evidence of bleeding diathesis or coagulopathy * Serious, non-healing wound, ulcer, or bone fracture * Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to enrollment; anticipation of need for major surgical procedure during the course of the study * Current, recent, or planned participation in an experimental drug study other than this Genentech-sponsored bevacizumab/erlotinib study * Progressive neurologic symptoms in subjects with a history of brain metastases * History of significant vascular disease (e.g., aortic aneurysm)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) | Approximately 3 years | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Prospectively Identified Treatment Emergent Adverse Events (TEAE) During Post-Chemotherapy Phase | Approximately 3 years | Treatment-related adverse events are defined as new events that occur following subject entry into the study or events that worsen following study entry state and are judged by the investigator to be possibly, probably or definitely related to study medication. Pulmonary hemorrhage, GI perforation, ATE events, proteinuria, CHF, and hypertension were prospectively identified TEAEs of grade \>=3. Data presented until cut-off date 28 January 2009. |
| Number of Participants With Any Adverse Events During Post-Chemotherapy Phase | Approximately 3.5 years | 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. |
| Number of Participants With Prospectively Identified Treatment Emergent Adverse Events (TEAE) During Chemotherapy Phase | Approximately 3 years | 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. |
| Incidence of Study Treatment Discontinuation | Approximately 3 years | 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. |
| Overall Survival | Approximately 3.5 years | Overall survival was defined as the length of time from randomization to death. |
| Incidence of Study Treatment Discontinuation for Reasons Other Than Disease Progression in Chemotherapy Phase | Approximately 3 years | Participants who experienced disease progression were discontinued from the study. Data presented up to data cutoff (18 July 2008). |
Countries
Argentina, Australia, Belgium, Brazil, Bulgaria, Hong Kong, Israel, Italy, Mexico, Philippines, Romania, Singapore, Spain, Taiwan, Thailand, United Kingdom, United States
Participant flow
Recruitment details
This study was conducted in 14 countries between 10 January 2006 and 19 June 2009.
Participants by arm
| Arm | Count |
|---|---|
| Bevacizumab + Placebo 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 | 373 |
| Bevacizumab + Erlotinib 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 | 370 |
| Total | 743 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Chemotherapy Phase | Adverse Event | 138 | 0 | 0 |
| Chemotherapy Phase | Disease progression | 139 | 0 | 0 |
| Chemotherapy Phase | Need for concomitant/ancillary therapy | 27 | 0 | 0 |
| Chemotherapy Phase | Patient's decision to discontinue | 35 | 0 | 0 |
| Chemotherapy Phase | Physician Decision | 28 | 0 | 0 |
| Chemotherapy Phase | Unrelated intercurrent illness | 3 | 0 | 0 |
| Chemotherapy Phase | Unwillingness or inability to comply | 6 | 0 | 0 |
| Post Chemotherapy Phase | Adverse Event | 0 | 34 | 38 |
| Post Chemotherapy Phase | Disease progression | 0 | 204 | 168 |
| Post Chemotherapy Phase | Lost to Follow-up | 0 | 0 | 1 |
| Post Chemotherapy Phase | Need for concomitant/ancillary therapy | 0 | 5 | 5 |
| Post Chemotherapy Phase | Not treated | 0 | 4 | 7 |
| Post Chemotherapy Phase | Patient's decision to discontinue | 0 | 4 | 8 |
| Post Chemotherapy Phase | Physician Decision | 0 | 8 | 11 |
| Post Chemotherapy Phase | Sponsor's decision to terminate study | 0 | 1 | 0 |
| Post Chemotherapy Phase | Unrelated intercurrent illness | 0 | 0 | 1 |
| Post Chemotherapy Phase | Unwillingness or inability to comply | 0 | 4 | 5 |
Baseline characteristics
| Characteristic | Bevacizumab + Placebo | Bevacizumab + Erlotinib | Total |
|---|---|---|---|
| Age, Continuous | 62.8 Years STANDARD_DEVIATION 10.8 | 62.9 Years STANDARD_DEVIATION 10.3 | 62.9 Years STANDARD_DEVIATION 10.6 |
| Sex: Female, Male Female | 177 Participants | 177 Participants | 354 Participants |
| Sex: Female, Male Male | 196 Participants | 193 Participants | 389 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 288 / 367 | 341 / 368 |
| serious Total, serious adverse events | 63 / 367 | 86 / 368 |
Outcome results
Primary
Progression-free Survival (PFS)
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
Population: Intent to treat (ITT) population included all participants who were randomized during the post-chemotherapy phase.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bevacizumab + Placebo | Progression-free Survival (PFS) | 3.7 months |
| Bevacizumab + Erlotinib | Progression-free Survival (PFS) | 4.8 months |
p-value: 0.000695% CI: [0.58, 0.864]Log Rank
Secondary
Incidence of Study Treatment Discontinuation
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
Population: Intent to treat (ITT) population included all participants who were randomized during the post-chemotherapy phase.. N= Number of participants analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bevacizumab + Placebo | Incidence of Study Treatment Discontinuation | Erlotinib/placebo: AE | 22 participants |
| Bevacizumab + Placebo | Incidence of Study Treatment Discontinuation | Bevacizumab: Unwillingness or inability to comply | 4 participants |
| Bevacizumab + Placebo | Incidence of Study Treatment Discontinuation | Erlotinib/placebo: Concomitant/ancillary therapy | 4 participants |
| Bevacizumab + Placebo | Incidence of Study Treatment Discontinuation | Bevacizumab: AE | 34 participants |
| Bevacizumab + Placebo | Incidence of Study Treatment Discontinuation | Erlotinib/placebo:Patient's Decision | 5 participants |
| Bevacizumab + Placebo | Incidence of Study Treatment Discontinuation | Bevacizumab: Unrelated intercurrent illness | 0 participants |
| Bevacizumab + Placebo | Incidence of Study Treatment Discontinuation | Erlotinib/placebo: Investigator's Decision | 6 participants |
| Bevacizumab + Placebo | Incidence of Study Treatment Discontinuation | Bevacizumab: Patient's Decision to Discontinue | 4 participants |
| Bevacizumab + Placebo | Incidence of Study Treatment Discontinuation | Erlotinib/placebo:Unwillingness/inability comply | 4 participants |
| Bevacizumab + Placebo | Incidence of Study Treatment Discontinuation | Bevacizumab: Sponsor's decision | 1 participants |
| Bevacizumab + Placebo | Incidence of Study Treatment Discontinuation | Erlotinib/placebo: Unrelated intercurrent illness | 0 participants |
| Bevacizumab + Placebo | Incidence of Study Treatment Discontinuation | Bevacizumab: Concomitant/ancillary therapy | 5 participants |
| Bevacizumab + Placebo | Incidence of Study Treatment Discontinuation | Erlotinib/placebo: Sponsor's decision | 1 participants |
| Bevacizumab + Placebo | Incidence of Study Treatment Discontinuation | Bevacizumab: Lost to follow-up | 0 participants |
| Bevacizumab + Placebo | Incidence of Study Treatment Discontinuation | Erlotinib/placebo: Lost to follow-up | 0 participants |
| Bevacizumab + Placebo | Incidence of Study Treatment Discontinuation | Bevacizumab: Investigator's Decision | 8 participants |
| Bevacizumab + Erlotinib | Incidence of Study Treatment Discontinuation | Erlotinib/placebo: Lost to follow-up | 1 participants |
| Bevacizumab + Erlotinib | Incidence of Study Treatment Discontinuation | Bevacizumab: AE | 38 participants |
| Bevacizumab + Erlotinib | Incidence of Study Treatment Discontinuation | Bevacizumab: Concomitant/ancillary therapy | 5 participants |
| Bevacizumab + Erlotinib | Incidence of Study Treatment Discontinuation | Bevacizumab: Patient's Decision to Discontinue | 8 participants |
| Bevacizumab + Erlotinib | Incidence of Study Treatment Discontinuation | Bevacizumab: Unwillingness or inability to comply | 5 participants |
| Bevacizumab + Erlotinib | Incidence of Study Treatment Discontinuation | Bevacizumab: Unrelated intercurrent illness | 1 participants |
| Bevacizumab + Erlotinib | Incidence of Study Treatment Discontinuation | Bevacizumab: Sponsor's decision | 0 participants |
| Bevacizumab + Erlotinib | Incidence of Study Treatment Discontinuation | Bevacizumab: Lost to follow-up | 1 participants |
| Bevacizumab + Erlotinib | Incidence of Study Treatment Discontinuation | Erlotinib/placebo: AE | 48 participants |
| Bevacizumab + Erlotinib | Incidence of Study Treatment Discontinuation | Erlotinib/placebo: Concomitant/ancillary therapy | 7 participants |
| Bevacizumab + Erlotinib | Incidence of Study Treatment Discontinuation | Erlotinib/placebo:Patient's Decision | 10 participants |
| Bevacizumab + Erlotinib | Incidence of Study Treatment Discontinuation | Erlotinib/placebo: Investigator's Decision | 12 participants |
| Bevacizumab + Erlotinib | Incidence of Study Treatment Discontinuation | Erlotinib/placebo:Unwillingness/inability comply | 2 participants |
| Bevacizumab + Erlotinib | Incidence of Study Treatment Discontinuation | Erlotinib/placebo: Unrelated intercurrent illness | 2 participants |
| Bevacizumab + Erlotinib | Incidence of Study Treatment Discontinuation | Erlotinib/placebo: Sponsor's decision | 0 participants |
| Bevacizumab + Erlotinib | Incidence of Study Treatment Discontinuation | Bevacizumab: Investigator's Decision | 11 participants |
Secondary
Incidence of Study Treatment Discontinuation for Reasons Other Than Disease Progression in Chemotherapy Phase
Participants who experienced disease progression were discontinued from the study. Data presented up to data cutoff (18 July 2008).
Time frame: Approximately 3 years
Population: Enrolled participants: All participants who were enrolled in the study. N= Number of participants analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bevacizumab + Placebo | Incidence of Study Treatment Discontinuation for Reasons Other Than Disease Progression in Chemotherapy Phase | Adverse Event | 54 participants |
| Bevacizumab + Placebo | Incidence of Study Treatment Discontinuation for Reasons Other Than Disease Progression in Chemotherapy Phase | Concomitant/ancillary therapy | 13 participants |
| Bevacizumab + Placebo | Incidence of Study Treatment Discontinuation for Reasons Other Than Disease Progression in Chemotherapy Phase | Patient's Decision to Discontinue | 16 participants |
| Bevacizumab + Placebo | Incidence of Study Treatment Discontinuation for Reasons Other Than Disease Progression in Chemotherapy Phase | Investigator's Decision | 13 participants |
| Bevacizumab + Placebo | Incidence of Study Treatment Discontinuation for Reasons Other Than Disease Progression in Chemotherapy Phase | Unwillingness or inability to comply with study | 4 participants |
| Bevacizumab + Placebo | Incidence of Study Treatment Discontinuation for Reasons Other Than Disease Progression in Chemotherapy Phase | Unrelated intercurrent illness | 1 participants |
| Bevacizumab + Erlotinib | Incidence of Study Treatment Discontinuation for Reasons Other Than Disease Progression in Chemotherapy Phase | Unwillingness or inability to comply with study | 0 participants |
| Bevacizumab + Erlotinib | Incidence of Study Treatment Discontinuation for Reasons Other Than Disease Progression in Chemotherapy Phase | Unrelated intercurrent illness | 0 participants |
| Bevacizumab + Erlotinib | Incidence of Study Treatment Discontinuation for Reasons Other Than Disease Progression in Chemotherapy Phase | Adverse Event | 40 participants |
| Bevacizumab + Erlotinib | Incidence of Study Treatment Discontinuation for Reasons Other Than Disease Progression in Chemotherapy Phase | Patient's Decision to Discontinue | 6 participants |
| Bevacizumab + Erlotinib | Incidence of Study Treatment Discontinuation for Reasons Other Than Disease Progression in Chemotherapy Phase | Investigator's Decision | 5 participants |
| Bevacizumab + Erlotinib | Incidence of Study Treatment Discontinuation for Reasons Other Than Disease Progression in Chemotherapy Phase | Concomitant/ancillary therapy | 6 participants |
| Carboplatin + Docetaxel | Incidence of Study Treatment Discontinuation for Reasons Other Than Disease Progression in Chemotherapy Phase | Investigator's Decision | 7 participants |
| Carboplatin + Docetaxel | Incidence of Study Treatment Discontinuation for Reasons Other Than Disease Progression in Chemotherapy Phase | Unwillingness or inability to comply with study | 0 participants |
| Carboplatin + Docetaxel | Incidence of Study Treatment Discontinuation for Reasons Other Than Disease Progression in Chemotherapy Phase | Adverse Event | 22 participants |
| Carboplatin + Docetaxel | Incidence of Study Treatment Discontinuation for Reasons Other Than Disease Progression in Chemotherapy Phase | Patient's Decision to Discontinue | 8 participants |
| Carboplatin + Docetaxel | Incidence of Study Treatment Discontinuation for Reasons Other Than Disease Progression in Chemotherapy Phase | Concomitant/ancillary therapy | 5 participants |
| Carboplatin + Docetaxel | Incidence of Study Treatment Discontinuation for Reasons Other Than Disease Progression in Chemotherapy Phase | Unrelated intercurrent illness | 1 participants |
| Cisplatin + Gemcitabine | Incidence of Study Treatment Discontinuation for Reasons Other Than Disease Progression in Chemotherapy Phase | Investigator's Decision | 3 participants |
| Cisplatin + Gemcitabine | Incidence of Study Treatment Discontinuation for Reasons Other Than Disease Progression in Chemotherapy Phase | Concomitant/ancillary therapy | 1 participants |
| Cisplatin + Gemcitabine | Incidence of Study Treatment Discontinuation for Reasons Other Than Disease Progression in Chemotherapy Phase | Patient's Decision to Discontinue | 5 participants |
| Cisplatin + Gemcitabine | Incidence of Study Treatment Discontinuation for Reasons Other Than Disease Progression in Chemotherapy Phase | Unrelated intercurrent illness | 1 participants |
| Cisplatin + Gemcitabine | Incidence of Study Treatment Discontinuation for Reasons Other Than Disease Progression in Chemotherapy Phase | Unwillingness or inability to comply with study | 1 participants |
| Cisplatin + Gemcitabine | Incidence of Study Treatment Discontinuation for Reasons Other Than Disease Progression in Chemotherapy Phase | Adverse Event | 14 participants |
| Other | Incidence of Study Treatment Discontinuation for Reasons Other Than Disease Progression in Chemotherapy Phase | Unwillingness or inability to comply with study | 1 participants |
| Other | Incidence of Study Treatment Discontinuation for Reasons Other Than Disease Progression in Chemotherapy Phase | Patient's Decision to Discontinue | 0 participants |
| Other | Incidence of Study Treatment Discontinuation for Reasons Other Than Disease Progression in Chemotherapy Phase | Concomitant/ancillary therapy | 2 participants |
| Other | Incidence of Study Treatment Discontinuation for Reasons Other Than Disease Progression in Chemotherapy Phase | Unrelated intercurrent illness | 0 participants |
| Other | Incidence of Study Treatment Discontinuation for Reasons Other Than Disease Progression in Chemotherapy Phase | Investigator's Decision | 0 participants |
| Other | Incidence of Study Treatment Discontinuation for Reasons Other Than Disease Progression in Chemotherapy Phase | Adverse Event | 8 participants |
Secondary
Number of Participants With Any Adverse Events During Post-Chemotherapy Phase
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
Population: Safety-evaluable randomized Participants: All randomized Participants who received at least one complete or partial dose of Bevacizumab + Erlotinib or Bevacizumab + Placebo. N= Number of participants analyzed. At the time of the 28 January 2009 data cutoff, an additional 25 patients had been randomized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bevacizumab + Placebo | Number of Participants With Any Adverse Events During Post-Chemotherapy Phase | 319 participants |
| Bevacizumab + Erlotinib | Number of Participants With Any Adverse Events During Post-Chemotherapy Phase | 353 participants |
Secondary
Number of Participants With Prospectively Identified Treatment Emergent Adverse Events (TEAE) During Chemotherapy Phase
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
Population: Safety-evaluable enrolled participants: All participants who enrolled and received at least one dose of chemotherapy or Bevacizumab. N= Number of participants analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bevacizumab + Placebo | Number of Participants With Prospectively Identified Treatment Emergent Adverse Events (TEAE) During Chemotherapy Phase | Proteinuria | 1 participants |
| Bevacizumab + Placebo | Number of Participants With Prospectively Identified Treatment Emergent Adverse Events (TEAE) During Chemotherapy Phase | Pulmonary hemorrhage | 6 participants |
| Bevacizumab + Placebo | Number of Participants With Prospectively Identified Treatment Emergent Adverse Events (TEAE) During Chemotherapy Phase | CHF | 3 participants |
| Bevacizumab + Placebo | Number of Participants With Prospectively Identified Treatment Emergent Adverse Events (TEAE) During Chemotherapy Phase | GI perforation | 6 participants |
| Bevacizumab + Placebo | Number of Participants With Prospectively Identified Treatment Emergent Adverse Events (TEAE) During Chemotherapy Phase | ATE events | 8 participants |
| Bevacizumab + Erlotinib | Number of Participants With Prospectively Identified Treatment Emergent Adverse Events (TEAE) During Chemotherapy Phase | Proteinuria | 5 participants |
| Bevacizumab + Erlotinib | Number of Participants With Prospectively Identified Treatment Emergent Adverse Events (TEAE) During Chemotherapy Phase | ATE events | 6 participants |
| Bevacizumab + Erlotinib | Number of Participants With Prospectively Identified Treatment Emergent Adverse Events (TEAE) During Chemotherapy Phase | GI perforation | 0 participants |
| Bevacizumab + Erlotinib | Number of Participants With Prospectively Identified Treatment Emergent Adverse Events (TEAE) During Chemotherapy Phase | CHF | 1 participants |
| Bevacizumab + Erlotinib | Number of Participants With Prospectively Identified Treatment Emergent Adverse Events (TEAE) During Chemotherapy Phase | Pulmonary hemorrhage | 2 participants |
| Carboplatin + Docetaxel | Number of Participants With Prospectively Identified Treatment Emergent Adverse Events (TEAE) During Chemotherapy Phase | ATE events | 2 participants |
| Carboplatin + Docetaxel | Number of Participants With Prospectively Identified Treatment Emergent Adverse Events (TEAE) During Chemotherapy Phase | Pulmonary hemorrhage | 3 participants |
| Carboplatin + Docetaxel | Number of Participants With Prospectively Identified Treatment Emergent Adverse Events (TEAE) During Chemotherapy Phase | GI perforation | 2 participants |
| Carboplatin + Docetaxel | Number of Participants With Prospectively Identified Treatment Emergent Adverse Events (TEAE) During Chemotherapy Phase | Proteinuria | 2 participants |
| Carboplatin + Docetaxel | Number of Participants With Prospectively Identified Treatment Emergent Adverse Events (TEAE) During Chemotherapy Phase | CHF | 1 participants |
| Cisplatin + Gemcitabine | Number of Participants With Prospectively Identified Treatment Emergent Adverse Events (TEAE) During Chemotherapy Phase | CHF | 0 participants |
| Cisplatin + Gemcitabine | Number of Participants With Prospectively Identified Treatment Emergent Adverse Events (TEAE) During Chemotherapy Phase | Pulmonary hemorrhage | 1 participants |
| Cisplatin + Gemcitabine | Number of Participants With Prospectively Identified Treatment Emergent Adverse Events (TEAE) During Chemotherapy Phase | Proteinuria | 2 participants |
| Cisplatin + Gemcitabine | Number of Participants With Prospectively Identified Treatment Emergent Adverse Events (TEAE) During Chemotherapy Phase | ATE events | 1 participants |
| Cisplatin + Gemcitabine | Number of Participants With Prospectively Identified Treatment Emergent Adverse Events (TEAE) During Chemotherapy Phase | GI perforation | 0 participants |
| Other | Number of Participants With Prospectively Identified Treatment Emergent Adverse Events (TEAE) During Chemotherapy Phase | ATE events | 0 participants |
| Other | Number of Participants With Prospectively Identified Treatment Emergent Adverse Events (TEAE) During Chemotherapy Phase | Proteinuria | 0 participants |
| Other | Number of Participants With Prospectively Identified Treatment Emergent Adverse Events (TEAE) During Chemotherapy Phase | Pulmonary hemorrhage | 2 participants |
| Other | Number of Participants With Prospectively Identified Treatment Emergent Adverse Events (TEAE) During Chemotherapy Phase | CHF | 0 participants |
| Other | Number of Participants With Prospectively Identified Treatment Emergent Adverse Events (TEAE) During Chemotherapy Phase | GI perforation | 0 participants |
Secondary
Number of Participants With Prospectively Identified Treatment Emergent Adverse Events (TEAE) During Post-Chemotherapy Phase
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
Population: Safety-evaluable randomized Participants: All randomized Participants who received at least one complete or partial dose of Bevacizumab + Erlotinib or Bevacizumab + Placebo. N= Number of participants analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bevacizumab + Placebo | Number of Participants With Prospectively Identified Treatment Emergent Adverse Events (TEAE) During Post-Chemotherapy Phase | Pulmonary hemorrhage | 2 participants |
| Bevacizumab + Placebo | Number of Participants With Prospectively Identified Treatment Emergent Adverse Events (TEAE) During Post-Chemotherapy Phase | GI perforation | 0 participants |
| Bevacizumab + Placebo | Number of Participants With Prospectively Identified Treatment Emergent Adverse Events (TEAE) During Post-Chemotherapy Phase | ATE events | 5 participants |
| Bevacizumab + Placebo | Number of Participants With Prospectively Identified Treatment Emergent Adverse Events (TEAE) During Post-Chemotherapy Phase | Proteinuria | 7 participants |
| Bevacizumab + Placebo | Number of Participants With Prospectively Identified Treatment Emergent Adverse Events (TEAE) During Post-Chemotherapy Phase | CHF | 1 participants |
| Bevacizumab + Placebo | Number of Participants With Prospectively Identified Treatment Emergent Adverse Events (TEAE) During Post-Chemotherapy Phase | Hypertension | 22 participants |
| Bevacizumab + Erlotinib | Number of Participants With Prospectively Identified Treatment Emergent Adverse Events (TEAE) During Post-Chemotherapy Phase | CHF | 3 participants |
| Bevacizumab + Erlotinib | Number of Participants With Prospectively Identified Treatment Emergent Adverse Events (TEAE) During Post-Chemotherapy Phase | Pulmonary hemorrhage | 3 participants |
| Bevacizumab + Erlotinib | Number of Participants With Prospectively Identified Treatment Emergent Adverse Events (TEAE) During Post-Chemotherapy Phase | Proteinuria | 7 participants |
| Bevacizumab + Erlotinib | Number of Participants With Prospectively Identified Treatment Emergent Adverse Events (TEAE) During Post-Chemotherapy Phase | GI perforation | 1 participants |
| Bevacizumab + Erlotinib | Number of Participants With Prospectively Identified Treatment Emergent Adverse Events (TEAE) During Post-Chemotherapy Phase | Hypertension | 23 participants |
| Bevacizumab + Erlotinib | Number of Participants With Prospectively Identified Treatment Emergent Adverse Events (TEAE) During Post-Chemotherapy Phase | ATE events | 8 participants |
Secondary
Overall Survival
Overall survival was defined as the length of time from randomization to death.
Time frame: Approximately 3.5 years
Population: Intent-to-treat population included all participants who were randomized during the post-chemotherapy phase.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bevacizumab + Placebo | Overall Survival | 13.3 months |
| Bevacizumab + Erlotinib | Overall Survival | 14.4 months |
p-value: 0.534195% CI: [0.698, 1.205]Log Rank