Long-term survival with systemic therapy in the last decade: Can melanoma be cured?

Abstract

Immune checkpoint inhibitors have been shown to prolong survival of patients with several types of cancer, and the finding was first established in melanoma. Previously, systemic therapy for advanced melanoma aimed only at tumor control and palliation of symptoms. However, in recent years, some patients who received systemic therapy have achieved a complete response and survived without continuous treatment for more than several years. This review discusses the long-term survival rates achieved with currently used systemic therapies and their future perspectives. Long-term survival is currently most likely to be achieved with the use of the standard-dose combination of nivolumab plus ipilimumab, however, this regimen is associated with a high frequency of serious or persistent immune-related adverse events. Several new anti-PD-1-based combination therapies with a better risk-benefit balance are currently under development. Although the acral and mucosal subtypes tend to be less responsive to immune checkpoint inhibitors, anti-PD-1-based combination therapy should continue to be investigated for these subtypes owing to its potential for better long-term survival. With the development of efficacious immunotherapy and targeted therapy, it is important to determine the optimal duration of systemic therapy to avoid unnecessary health and financial burdens as well as to improve efforts to support long-term cancer survivors. As the goal of systemic therapy shifts from tumor control to long-term survival, in future clinical trials, long-term clinical outcomes should be evaluated to assess the benefits of novel agents.

Keywords: BRAF; immunotherapy; melanoma; survival; targeted therapy.