A phase II trial of bevacizumab in patients with recurrent solid tumor brain metastases who have failed whole brain radiation therapy (WBRT).

2070 Background: Brain metastases (BM) are the most common intracranial malignancy with overall a poor prognosis estimated at approximately 4 months from time of initial diagnosis for treated patients, and even lower after failing WBRT after which treatment options have been limited and outcomes poor. Methods: This is an open label phase 2 study where patients who have previously failed WBRT received bevacizumab at a dose of 10 mg/kg intravenously every two weeks until CNS disease progression with one cycle being defined as 4 weeks. The primary endpoint was objective radiographic tumor response as defined by modified Response Assessment in Neuro-oncology (RANO) criteria. Secondary endpoints included progression free survival (PFS) at 6 months, time to progression, time to response, duration of response, overall survival (OS), quality of life (QOL) as measured by the FACT-G and FACT-Br and safety. Results: A total of 27 patients were consented and registered to study of which 24 were evaluable for ORR (3 came off study prior to first follow up MRI brain). Medianage was 53 (range 27-73), median number of cycles was 5.5 (range 1-20) with a median follow up of 8.7 months (range 2.4-47.9mo). Of the 24evaluable patients, there were 6 Partial response, 16 stable disease and 2progressive disease. The 6 month PFS: 46% (95% CI: 25% - 67%) and median PFS was 5.3 months. Median OS was 9.5 months (95% confidence interval 6.3m – 15.0m). For the patients who completed sequential QOL assessments, there was no significant decline in QOL but there was a nonsignificant improvement in the FACT-Br scores. Overall, treatment was well tolerated with 3grade 3 adverse events seen: hypertension (n = 3), headache (n = 1) and thrombotic event (n = 1). Conclusions: For this WBRT failure BM population, we were able to show a 25% disease response to bevacizumab therapy along with good drug tolerability and no noted central nervous system bleeding. Improved survival as compared to historical controls was seen 9.5 m. Of the 24 evaluable patients, 81% (22/24) experienced clinical benefit defined as stable disease or better. Bevacizumab therapy could be a viable option for solid tumor BM patients who experience progression following WBRT, however a larger trial is required to confirm this data. Clinical trial information: NCT01898130.