Treatment Options for Advanced Melanoma After Anti-PD-1 Therapy

Abstract

Purpose of review: While anti-PD-1 antibodies have been a breakthrough in the treatment of patients with advanced melanoma, a substantial proportion of patients are still refractory to or progress after treatment with anti-PD-1 immunotherapy. Here, we review the post anti-PD-1 therapy alternatives that may be possible for patients with unresectable or metastatic stage 3 or 4 melanoma.

Recent findings: Currently available treatment options include BRAF-targeted and MEK inhibitor-targeted therapies for those with BRAFV600 mutant melanoma, while for patients with BRAF-WT melanoma or those who have already received prior BRAF-targeted therapy, options include anti-CTLA-4 therapy, alone or in combination with anti-PD-1 therapy, or for selected patients, clinical trials that may incorporate other immune checkpoint inhibitors or co-stimulatory agonists, oncolytic virotherapies, adoptive cellular therapies, or other novel agents. Participation in clinical trials is critical in order to delineate what more effective treatment options are and which group of patients after receiving prior anti-PD-1 therapy.

Keywords: Anti-PD-1; BRAF; Checkpoint inhibitors; Immunotherapy; Ipilimumab; MEK; Melanoma; Resistance; T-VEC.