Bevacizumab is effective for the treatment of
non-small cell lung cancer (NSCLC). Ongoing trials are exploring the safety of
bevacizumab in patients with inactive, previously treated
brain metastases. However,
bevacizumab safety and efficacy in the treatment of active
brain metastases is unknown.
Bevacizumab received accelerated FDA approval for progressive
glioblastoma, a
primary brain tumor, because of high response rates and low incidence of
intracranial hemorrhage. We retrospectively identified patients treated with
bevacizumab for active (treatment naïve or progressive) central nervous system (CNS)
metastases from NSCLC. MRI scans performed at least 6 weeks after initiating
bevacizumab were assessed for response. There were six patients, four women and two men with a median age of 60 years (range 59-77) at initiation of
bevacizumab. Five patients had progressive CNS
metastases despite prior treatment including surgery,
radiotherapy, and/or
chemotherapy; one patient had treatment-naïve
brain metastases. Two patients had leptomeningeal
metastases, isolated or coexistent with parenchymal
brain metastases in one patient each.
Bevacizumab was administered alone to one patient and in combination with various cytotoxic
chemotherapies in the others. Toxicity included an asymptomatic (Grade 1) intra-tumoral
hemorrhage which occurred in one of three patients receiving concurrent anticoagulation with
bevacizumab. There was no recurrent CNS
bleeding in two patients with a prior history of such
hemorrhage. Best CNS response (RECIST) was partial in two, stable disease in three, and progression in one. Median progression-free survival (PFS) was 7.8 months and median overall survival (OS) was 14.1 months following initiation of
bevacizumab. Clinical benefit was also observed in the form of improved symptoms and reduced
corticosteroid requirements.
Bevacizumab should be used with caution in patients with active CNS
metastases pending additional safety data. This series suggests
bevacizumab may be safe and effective for progressive
brain metastases from NSCLC and deserves further study.