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.

Inclusion Criteria:

• Signed informed consent
• Histologically or cytologically confirmed NSCLC except for squamous cell carcinoma
• Treated brain metastases without evidence of progression or hemorrhage after treatment, as ascertained by clinical examination and brain imaging (MRI or CT) during the screening period
• Appropriateness for first- or second-line systemic therapy for advanced NSCLC
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Age ≥ 18 years
• For women of childbearing potential and sexually active males, use of an accepted and effective method of contraception (e.g., hormonal or barrier methods, abstinence) prior to study entry and for the duration of the study

Exclusion Criteria:

• Brain biopsy/neurosurgical procedure performed within 3 months prior to Day 1
• Progressive neurologic symptoms
• Active malignancy other than lung cancer
• Current, recent, or planned participation in an experimental drug study
• Prior treatment with an investigational or marketed agent that acts by anti-angiogenesis mechanisms
• Gross hemoptysis within 3 months prior to Day 1
• Inadequately controlled hypertension
• Unstable angina or New York Heart Association Grade II or greater congestive heart failure (CHF)
• Abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to Day 1
• Myocardial infarction within 6 months prior to Day 1
• Stroke within 6 months prior to Day 1
• Active symptomatic peripheral vascular disease within 6 months prior to Day 1
• History of significant vascular disease
• Evidence of bleeding diathesis or coagulopathy
• Known hypersensitivity to any components of bevacizumab
• Inadequate organ function
• Serious non-healing wound, ulcer, or bone fracture
• Urine protein/creatinine (UPC) ratio of ≥ 1.0
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1, or anticipation of need for major surgical procedure during the course of the study
• Pregnancy or lactation
• Known evidence of disseminated intravascular coagulation (DIC)
• Active infection or fever > 38.5°C within 3 days prior to Day 1
• Any other medical condition (including mental illness or substance abuse) deemed by the clinician to be likely to interfere with a patient's ability to sign informed consent, cooperate and participate in the study, or interfere with the interpretation of the results