Survival patterns following brain metastases for patients with melanoma in the targeted therapy era.

Abstract

9064 Background: Survival from metastatic melanoma (MM) has been significantly prolonged with the introduction of molecularly targeted therapy, including BRAF inhibitors (BRAFi) for patients (pts) with the V600E mutation. Here, we present the first data describing patterns of survival after diagnosis of brain metastases (BM) in a large cohort of these pts with long follow-up. Methods: A retrospective review of 191 MM pts accrued on multiple prospective trials between 2008–2012 was conducted. These trials assessed novel immunologic and targeted therapies in pts with both BRAF mutant (n=70) and wild type/unknown (n=121) tumors. We evaluated pt characteristics and the impact of systemic and BM-directed treatments. Results: Of 98 pts who developed BM, median follow-up after first BM was 7.7 months (15.5 months for the 25 living pts), and 33 were treated with BRAFi. Median duration of BRAFi use was 5.9 months (range 0.7–27.1), which preceded BM in 30%, was concurrent with first BM in 18%, and followed first BM in 52%. Ipilimumab or anti–PD-1/PD-L1 immunotherapy was given to 58% of pts who received a BRAFi and 95% of those who did not. Limited intracranial disease on initial BM presentation (defined as ≤3 lesions) occurred in 70% of BRAFi-treated pts and 74% of non-BRAFi pts, and 70% of BRAFi pts received at least one focal BM treatment (stereotactic radiosurgery or resection) compared to 75% of non-BRAFi pts. As shown in the Table, actuarial survival after BM diagnosis was prolonged among pts treated with a BRAFi. This is due primarily to the nearly 2-year median survival of pts for whom a BRAFi was initiated after BM were diagnosed. Conclusions: Survival for pts with BM from BRAF mutant MM can significantly exceed the often anticipated 4–6 months, particularly if a BRAFi is initiated after BM arise. This supports BRAFi activity in intracranial disease, and helps to inform trials currently under way testing BRAFi use among MM pts with previously diagnosed BM. [Table: see text]