Combinatorial Approaches to the Treatment of Advanced Melanoma

Abstract

The treatment landscape for patients with advanced melanoma has dramatically improved over the past decade, leading to unprecedented survival. Despite the robust activity of single-agent immune-checkpoint blockade with anti-CTLA-4 or anti-PD-1 agents, and the efficacy of targeted therapies capable of interrupting aberrant signaling resulting from BRAF mutations, the benefit from these therapies is not universal. Advanced understanding of immune and molecular processes underlying melanoma tumorigenesis has demonstrated the promise of combined, multidrug regimens. We discuss the currently available evidence that supports using combinatorial approaches in advanced melanoma treatment and provide insights into promising new combination strategies under investigation.

Keywords: BRAF; Immunotherapy; MAPK; Melanoma.

Figure 1.

Overview of proposed treatment algorithms involving combinatorial approaches for patients with advanced melanoma. Dabra – dabrafenib / Tram – trametinib / Vem – vemurafenib / Cobi – cobimetinib / Enco – encorafenib / Bini – binimetinib / Ipi/Nivo – ipilimumab 3mk/kg + nivolumab 1mg/kg / “low-dose”- ipilimumab 1mg/kg + nivolumab 3mg/kg / * - for patients with symptomatic CNS metastases or using steroids, the optimal approach remains unclear / ** - in these scenarios, single-agent anti-PD-1 is also an acceptable alternative, particularly in select situations (underlying autoimmune diseases, comorbidities, etc.)