Triplet Therapy in Melanoma — Combined BRAF/MEK Inhibitors and Anti-PD-(L)1 Antibodies
Julia Dixon‐Douglas, Riyaben P. Patel, Pretashini M Somasundram, Grant A. McArthur
Abstract
PURPOSE OF REVIEW: We provide an updated review of clinical trials evaluating the combination of BRAF/MEK inhibitors with anti-PD-(L)1 therapy (triplet therapy) for patients with advanced BRAF-mutant melanoma, accompanied by a summary of the biological evidence supporting this combination. RECENT FINDINGS: Resistance to BRAF/MEK inhibition and comparatively low response rates to immune checkpoint inhibitors remain clinical challenges in the treatment of melanoma. Preclinical data demonstrates that targeted therapy is immune-modulatory and synergises with immune checkpoint inhibition. Several randomised controlled trials have evaluated the combination of targeted therapy with immune checkpoint inhibition. Triplet therapy has shown improvements in progression-free survival and durability of response compared to BRAF/MEK inhibition alone; however, questions remain regarding the best clinical scenario for implementation of this regimen in the era of front-line immunotherapy.