Is single versus combination therapy problematic in the treatment of cutaneous melanoma?

: The development of immunotherapies and targeted therapies has changed the treatment approach in resectable, nonresectable, and metastatic melanoma. Because of their different pharmacological profiles, immunotherapies and/or targeted therapies have been studied in various combinations. : We reviewed PubMed for most important clinical trials investigating efficacy and tolerability of combinatorial and single-agent approaches for the treatment of melanoma that were published up to June 2019. We discuss the most promising therapy approaches and highlight challenges of melanoma treatment. : Combinatorial approaches seem to be very promising in the treatment of resectable and advanced melanoma. Currently, dual immune checkpoint inhibition (ICI) with nivolumab and ipilimumab offers the best first-line treatment option for patients with -wt and -mutated, advanced melanoma. It is therapy of choice in younger patients with good ECOG performance status and poor prognostic features, whereas ICI monotherapy should be preferred in elderly patients with advanced melanoma. Benefit-risk ratio, patient's QoL and expectations, as well as treatment costs have to be considered in the choice of treatment. However, to elucidate mechanisms of resistance, biomarkers of response and to better define personalized strategies in the treatment of cutaneous melanoma, larger clinical trials comparing combined versus sequential therapies are necessary.