Efficacy of BRAF Inhibitors in Asian Metastatic Melanoma Patients: Potential Implications of Genomic Sequencing in BRAF-Mutated Melanoma

Abstract

BACKGROUND: The BRAF inhibitors vemurafenib and dabrafenib are currently the standard treatment for metastatic melanoma with BRAF V600 mutations. However, given the rarity of noncutaneous melanoma, including acral and mucosal subtypes, the efficacy of BRAF inhibitors for this subset of patients has not been extensively investigated. Acquired resistance generally appears 6 to 8 months after treatment with a BRAF inhibitor, and the mechanism of resistance is not well established. METHODS: We examined treatment outcomes for patients diagnosed with metastatic melanoma and treated with BRAF inhibitors at Samsung Medical Center between April 2013 and December 2015. We analyzed genomic alterations in selected patients using targeted sequencing. RESULTS: Twenty-seven patients with a median age of 49 years (range 23-82 years) with metastatic melanoma and treated with a BRAF inhibitor were identified. Of these patients, 19 (70.3%) had noncutaneous melanoma, including acral and mucosal melanoma. All patients had BRAFV600E mutations. The median progression-free survival of all patients was 9.2 months (95% confidence interval, 1.6-16.7), and the objective response rate was 78.9% in the mucosal/acral melanoma group and 75.0% in the cutaneous melanoma group. Three (11.1%) patients achieved complete response, and 19 (70.4%) showed a partial response. Targeted sequencing in five patients demonstrated NF1 mutations in three patients who did not respond to BRAF inhibitors. CONCLUSION: BRAF inhibitors were an effective therapeutic option for Korean patients with metastatic melanoma harboring a BRAF V600 mutation regardless of melanoma subtype (acral/mucosa versus cutaneous).