The Role of Neoadjuvant Therapy in Melanoma

Neoadjuvant therapy in melanoma is an area of active investigation with numerous completed and ongoing trials studying a variety of therapeutic interventions utilizing diverse designs. Here, we review completed and ongoing neoadjuvant trials in melanoma, discuss endpoint assessment, and highlight biomarker development in this context.

High-risk resectable melanoma with clinically detectable lymph node (LN) with or without in-transit and/or satellite metastases represent ~ 20% of melanoma patients and have a high risk of relapse despite definitive surgery. Adjuvant therapy with anti-PD-1 immunotherapy or BRAF/MEK-targeted therapy has improved relapse-free survival (RFS) and overall survival (OS) in large phase III trials and is approved for this indication. However, despite surgery and adjuvant therapy, many patients relapse and/or experience treatment-related toxicity, underscoring the need to identify and understand mechanisms of response and resistance. In melanoma, neoadjuvant therapy is an active area of research with numerous completed and ongoing trials utilizing FDA-approved and novel agents with intriguing results. Neoadjuvant therapy for regionally metastatic disease is an established standard in multiple cancers, where it has been shown to improve operability, facilitate biomarker development, and even is a registrational endpoint for drug development in breast cancer. Recently, a spate of neoadjuvant studies in melanoma has looked at a swathe of agents with promising clinical and biomarker results. Coordinated efforts are underway to translate these findings to earlier stage disease while prioritizing the evaluation of new strategies in unresectable disease.