title: Efficacy and safety of bevacizumab in active brain metastases from non-small cell lung cancer.
abstract: 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.
authors.affiliation: Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Kevin C
authors.initials: KC
authors.lastname: De Braganca
authors.forename: Yelena Y
authors.initials: YY
authors.lastname: Janjigian
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Azzoli
authors.forename: Mark G
authors.initials: MG
authors.lastname: Kris
authors.forename: Maria C
authors.initials: MC
authors.lastname: Pietanza
authors.forename: Craig P
authors.initials: CP
authors.lastname: Nolan
authors.forename: Antonio M
authors.initials: AM
authors.lastname: Omuro
authors.forename: Andrei I
authors.initials: AI
authors.lastname: Holodny
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Lassman
mesh_terms: D000368:Aged; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use* / Q000633:toxicity; D000911:Antibodies, Monoclonal / Q000627:therapeutic use* / Q000633:toxicity; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000556:secondary*; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies
chemical_list: D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab