Novel Therapies for Metastatic Melanoma: An Update on Their Use in Older Patients

Abstract

Cutaneous melanoma is the most aggressive form of skin cancer. With age as a risk factor, melanoma is projected to become a substantial healthcare burden. The clinical course of melanoma in older patients is different from that in middle-aged and younger patients: melanomas are thicker, have higher mitotic rates and are more likely to be ulcerated. Older patients also have a higher mortality rate, yet, paradoxically, have a lower rate of lymph node metastases. After decades of no significant progress in the treatment of this devastating disease, novel insights into the mechanisms underlying the pathophysiology of metastatic melanoma have led to new and remarkably efficient therapeutic opportunities. The discovery that about half of all melanomas carry BRAF mutations led to the introduction of targeted therapy with significant improvements in clinical outcomes. Although these drugs appear to be equally effective in older patients, specific considerations regarding adverse events are required. Besides targeted therapy, immunotherapy has emerged as an alternative therapeutic option. Antibodies that block cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed cell death protein 1 (PD-1) can induce responses with high durability. Despite an aging immune system, older patients seem to benefit to the same degree from these treatments, apparently without increased toxicity. In this review, we focus on the epidemiology, clinicopathological features, and recent developments of systemic treatment in cutaneous melanoma with regard to older patients.