PD-1 and PD-L1 inhibitors in melanoma treatment: past success, present application and future challenges

Abstract

Anti-programmed death (PD)-1 antibodies have now become the standard of care for advanced melanoma, with two drugs gaining US FDA approval in recent years: nivolumab and pembrolizumab. Both have demonstrated significant activity and durable response with a manageable toxicity profile. Despite initial success, ongoing challenges include patient selection and predictors of response, innate resistance and optimizing combination strategies. In this overview, we take a closer look at the history and development of therapeutic targets to the PD-1/PD-ligand (L)1 pathway, clinical evidence, availability of biomarkers and their limitations in clinical practice and future strategies to improve treatment outcomes.

Keywords: biomarkers; immunotherapy; ipilimumab; melanoma; nivolumab; pembrolizumab; programmed death ligand-1; programmed death-1; tumor-infiltrating lymphocytes.