Current and emerging treatment options for BRAFV600-mutant melanoma.

Abstract

Introduction: BRAF mutations are the most common driver mutation in cutaneous melanoma, present in 40% of cases. Rationally designed BRAF targeted therapy (TT) has been developed in response to this, and alongside immune checkpoint inhibitors (ICI), forms the backbone of systemic therapy options for BRAF-mutant melanoma. Various therapeutic approaches have been studied in the neoadjuvant, adjuvant and advanced settings, and there is a wealth of information to guide clinicians managing these patients. Despite this, certain challenges remain.

Areas covered: We reviewed the available literature regarding BRAF mutation types and resistance mechanisms, neoadjuvant and adjuvant approaches for patients with early-stage disease, management of advanced disease, including patients with brain metastases, as well as identified areas of further research.

Expert opinion: Although there is a significant amount of literature to guide the management of BRAF-mutant melanoma, several questions remain. Thus far, the management of stage III BRAF-mutant patients following neoadjuvant ICI, treatment de-escalation in long-term TT responders in the advanced setting and the management of symptomatic brain metastases remain areas of debate. Further work on predictive and prognostic biomarkers for patients with BRAF-mutant melanoma patients will assist in clinical decision-making.