This was an open-label, multicenter, single-arm, Phase II trial of bevacizumab combined with first- or second-line therapy in patients with metastatic non-squamous non-small cell lung cancer (NSCLC) with previously treated central nervous system (CNS) metastases. A total of 115 patients enrolled in the study.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
115
15 mg/kg intravenously (IV) on the first day of each 21- to 28-day cycle (± 4 days); the interval between infusions could not be \< 17 days, but could extend beyond 28 days if chemotherapy was delayed to allow recovery from toxicity.
Carboplatin, cisplatin, paclitaxel, docetaxel, gemcitabine, vinorelbine, pemetrexed, or erlotinib administered on Day 1 of every 21-day cycle except gemcitabine, which was administered on Days 1 and 8 of every cycle. Agents were administered as a platinum doublet, or erlotinib alone, at the investigator's discretion. Chemotherapy was administered for a total of 6 planned cycles (up to 8 cycles with prior approval from the Medical Monitor), followed by single-agent bevacizumab therapy. The chemotherapy regimen was to be consistent throughout the study. Erlotinib was administered orally daily. All agents were dosed and administered per institutional standards using the respective package insert as a guideline.
Percentage of Participants With Symptomatic National Cancer Institute's Common Terminology Criteria for Adverse Events v3.0 (NCI CTCAE) Grade ≥2 Central Nervous System (CNS) Hemorrhage
The percentage of participants with symptomatic NCI CTCAE Grade ≥ 2 CNS hemorrhage, defined as the presence of clinical symptoms determined by the investigator to be directly referable to a Grade ≥ 2 CNS hemorrhage. Grade 1: Asymptomatic, radiographic findings only Grade 2: Medical intervention indicated Grade 3: Ventriculostomy, intracranial pressure (ICP) monitoring, intraventricular thrombolysis, or operative intervention indicated Grade 4: Life-threatening consequences; neurologic deficit or disability Grade 5: Death
Time frame: From the first administration of bevacizumab until 60 days after discontinuation of bevacizumab treatment was reported (up to 2 years)
Overall Survival (OS) in First-line Setting
To assess overall survival in the subset of subjects treated in the first-line setting with bevacizumab plus either chemotherapy or erlotinib for non-squamous NSCLC with previously treated brain metastases.
Time frame: Time from enrollment to death from any cause (up to 2 years)
Number of Participants With Overall Survival (OS) in First-line Setting [1-Year or More Survival]
Number of Participants with overall survival in the subset of subjects treated in the first-line setting with bevacizumab plus either chemotherapy or erlotinib for non-squamous NSCLC with previously treated brain metastases.
Time frame: Time from enrollment to death from any cause (up to 2 years)
OS in First-line and Second-line Settings
To assess overall survival in the subset of subjects treated in the first-line setting with bevacizumab plus either chemotherapy or erlotinib for non-squamous NSCLC with previously treated brain metastases.
Time frame: Time from enrollment to death from any cause (up to 2 years)
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Erlotinib, pemetrexed, docetaxel, or chemotherapy at the investigator's discretion. Erlotinib was administered orally daily; pemetrexed and docetaxel were administered IV on Day 1 of every 21-day cycle. Single-agent bevacizumab therapy could be continued at the investigator's discretion if the second-line agent was discontinued. All agents were dosed and administered per institutional standards using the respective package insert as a guideline.
Number of Participants With OS in First-line and Second-line Settings [1-Year or More Survival]
To assess the number of participants with overall survival in the subset of subjects treated in the first-line setting with bevacizumab plus either chemotherapy or erlotinib for non-squamous NSCLC with previously treated brain metastases.
Time frame: Time from enrollment to death from any cause (up to 2 years)
Number of Participants With Selected Adverse Events
Number of participants with selected adverse events (all grades based on NCI CTCAE) included any grade CNS hemorrhage, any grade pulmonary hemorrhage, any grade gastrointestinal (GI) perforation, Grade ≥ 2 arterial thromboembolic event, Grade ≥ 2 left ventricular systolic dysfunction, Grade ≥ 3 non-CNS non-pulmonary hemorrhage, Grade ≥ 3 proteinuria, Grade ≥ 3 proteinuria, Grade ≥ 3 hypertension, any serious adverse event\*, and any adverse event leading to study treatment discontinuation. \*For serious adverse events, please see Adverse Event Reporting Section.
Time frame: From start of bevacizumab treatment to 60 days following discontinuation of bevacizumab (up to 2 years)