Current and emerging treatment options for BRAFV600-mutant melanoma

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.

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.

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.