Safety of bevacizumab (B) and erlotinib (E) therapy in patients (pts) with treated brain metastases (mets) in the phase III, placebo (P)-controlled, randomized BeTa trial for pts with advanced non-small cell lung cancer (NSCLC) after failure of standard first-line chemotherapy

Abstract

e19025 Background: Bevacizumab (B) + carboplatin/paclitaxel received FDA approval in 10/06 for improving survival in first-line treatment of advanced NSCLC patients (pts). In the past, pts with brain mets had been excluded from trials of B due to concerns about the possibility of CNS hemorrhage. We report on the safety of B therapy in combination with E in a subset of pts with treated brain mets who enrolled in the BETA lung study for NSCLC. Methods: Pts in the subset had recurrent advanced stage NSCLC. Their disease at enrollment included brain mets previously treated with whole brain radiation therapy. Neurosurgery and stereotactic radiosurgery were permissible in addition to WBRT. Patients with an ongoing requirement for dexamethasone treatment and those who had previously been treated with anti-angiogenesis or epidermal growth factor receptor-targeted therapy were not eligible. Pts were treated with E+B or E+P. E dosing was at 150 mg daily; B/P dosing was 15mg/kg intravenous every (q) 3 weeks. Responses were evaluated q 6 wks until wk 24 and every 12 wks thereafter. Treatment continued until disease progression. Results: 68 pts with brain metastases were enrolled between June 2005 and April 2008. 37 pts received E+B and 31, E +P, with median treatment durations of 2.6 and 2.7 months respectively. No CNS hemorrhages or Gr 3+ bleeding events were reported among these pts. 3 Gr 3–4 nervous system adverse events (AE) were reported in each arm. One convulsion, one case of memory impairment and one case of toxic encephalopathy was reported in the E+P arm and a case of ataxia, headache, and cerebral ischemia were reported in the E+B arm. Conclusions: 37 pts with previously treated brain mets were treated with E+B in the BETA study. No CNS hemorrhages were reported in this subset and no new safety signals identified. The treatment duration for subjects with metastasis was equivalent in the E+B and E+ P arms. These data suggest an acceptable safety profile for the subset of patients with brain mets treated with B in the BETA lung study. [Table: see text]