Is There an Optimal Intersection for Targeted and Immunotherapy Treatments for Melanoma

Melanoma therapeutics have undergone massive changes with the approval of BRAF and MEK kinase inhibitors and immune-checkpoint blocking antibodies against CTLA-4 and PD-1. Targeted and immunotherapy have different strengths and weaknesses, but both are essential to clinical management of patients with advanced mela- noma. Kinase inhibitors have rapid and high response rates, though their benefit is modest in terms of progres- sion-free survival. Immunotherapy generally has low- er response rates and can manifest atypical treatment kinetics. However, immunotherapy may offer a more robust potential for durable tumor control. Overall sur- vival has been improved by both approaches, and next steps in clinical research will focus on how to combine these modalities. Early combination clinical trials have suggested that a cautious approach is appropriate when combining kinase inhibitors with immunotherapy. To fur- ther explore this, rigorous biomarker-driven clinical trials are essential. Beyond just melanoma, it seems likely that both combinations and sequenced approaches of target- ed and immunotherapies will be required to harness the full potential of these approaches for treatment of cancer.