The Prognostic Value of BRAF, C-KIT, and NRAS Mutations in Melanoma Patients With Brain Metastases

Abstract

Brain metastases are a common problem in patients with melanoma, but little is known about the effect of gene mutations on survival in these patients. We created a retrospective multi-institutional database of 823 patients with melanoma and brain metastases diagnosed between 2006 and 2015. Clinical parameters, gene mutation status (BRAF, C-KIT, NRAS), and treatment were correlated with survival. Treatment patterns and outcomes were compared with a prior era (1985-2005). BRAF status was known in 584 of 823 patients (71%). BRAF, NRAS, and C-KIT mutations were present in 51%, 22%, and 11% of tested patients, respectively. The median time from primary diagnosis to brain metastasis was 32months, and overall median survival (MS) from the time of initial treatment of brain metastases was 10months. MS for BRAF-positive and BRAF-negative patients was 13months and 9months, respectively (P=.02). There was no significant difference in MS in patients with or without NRAS or C-KIT mutations. The time from primary diagnosis to brain metastasis did not vary by mutation and was not associated with survival after the diagnosis of brain metastases. MS for the 1985 to 2005 and 2006 to 2015 cohorts was 6.7months and 10.0months, respectively (P<.01). Reflecting treatment-trend changes, use of whole-brain radiation therapy decreased from 48% to 26% during this period. Among BRAF-positive patients, 71% received targeted BRAF and/or MEK inhibitors and 57% received some combination of targeted therapy, chemotherapy, and/or immunotherapy. For melanoma patients with brain metastases, BRAF-positive patients survive longer than BRAF-negative patients and overall survival has improved from 1985-2005 to 2006-2015.