Non-classical BRAF melanoma: A retrospective review of disease characteristics and prognostic implications.

Abstract

e21060 Background: Activating mutations in the BRAF gene occur in 40-60% of melanomas with the majority of mutations resulting in V600E/K. Previous cohort studies have identified rates of non-V600E/K BRAF mutations to occur in 5-12% of patients. Despite this, there remains limited evidence characterizing the disease characteristics and outcomes of patients who harbor the non-classical BRAF mutation. Methods: Retrospective review of all melanoma patients treated at a tertiary cancer center that had BRAF mutation testing through targeted sequencing. Three groups of patients were identified and compared with respect to patient and disease characteristics: a) BRAF negative; b) BRAF V600E/K positive; c) BRAF non-V600E/K positive. Results: BRAF testing was performed in 168 melanoma patients of which 101 (60%) were BRAF negative; 55 (33%) were BRAF V600E/K positive; 12 (7%) were BRAF non-V600E/K positive (2 G466E, 1 of each G469E, K601N, K601E, L597Q, L597S, V741I, N594G, D594N, V600R and 1 with both K601N & V600E). Of these, 147 patients had baseline demographic and treatment data available for analysis. BRAF mutations were more common among males (45.6% of men vs. 22.7% of women, p = 0.03). No significant differences between other baseline patient demographics noted. Pathological characteristics revealed a non-significant trend toward poorer prognostic factors with BRAF non-V600E/K patients having increased Breslow depth (7.0 mm vs. 5.0 mm BRAF negative, 4.3 mm BRAF V600E/K) and higher rates of ulceration (71% vs. 44% BRAF negative, 30% BRAF V600E/K). BRAF non-V600E/K patients displayed a non-significant trend toward poorer overall survival (71 months vs. 215 months BRAF negative, 125 months BRAF V600E/K). Conclusions: Non-V600E/K BRAF positive patients appear to display less favorable disease characteristics and outcomes as compared to BRAF negative and BRAF V600E/K positive patients. Non-V600E/K melanoma show limited response to BRAF targeted therapy; however, evidence suggests the presence of non-classical mutations may confer susceptibility to MEK inhibition. Further characterization of non-V600E/K BRAF melanoma may allow for more refined prognostication and treatment decisions.