Sequencing Targeted and Immune Therapy in BRAF-Mutant Melanoma: Lessons Learned

The treatment strategy for BRAF-mutated melanoma remains unsatisfactory, although the advent of immune checkpoint inhibition has improved the prognosis of advanced melanoma. This article reports current evidence on the efficacy and safety of sequential immunotherapy with targeted therapy in patients with BRAF-mutated melanoma. It discusses criteria for the use of available options in clinical practice.

Targeted therapy provides rapid disease control in a relatively high proportion of patients, although the development of secondary resistance limits the duration of responses; in contrast, immunotherapy may induce slow but more durable responses in a subset of patients. Therefore, the identification of a combination strategy for the use of these therapies seems a promising perspective. Currently, inconsistent data have been obtained, but most studies indicate that the administration of BRAFi/MEKi prior to immune checkpoint inhibitors appears to reduce the efficacy of immunotherapy. On the contrary, several clinical and real-life studies suggest that frontline immunotherapy with subsequent targeted therapy may be associated with better tumor control than immunotherapy alone. Larger clinical studies are ongoing to confirm the efficacy and safety of this sequencing strategy for treating BRAF-mutated melanoma with immunotherapy followed by targeted therapy.