Treatment Options for Relapsed Metastatic Cutaneous Melanoma

Publication date: Jul 10, 2025

For patients with clear molecular targets, such as BRAF mutations, the preferred next step after progression on checkpoint inhibitors is often dual targeted therapy with BRAF and MEK inhibitors. For select patients with limited, injectable disease without visceral metastases, oncolytic virus therapy remains a valuable tool, although long-term cures are rare. Although regulatory agencies focus on end points such as progression-free survival and objective response rate to evaluate new therapies, clinicians prioritize patient-centered outcomes and overall survival. After frontline therapy for melanoma, treatment options continue to expand but are not yet fully defined. Clinical judgment often guides off-label use based on individual patient response and tolerance. Patients often accept higher toxicity levels in pursuit of long-term remission, emphasizing the importance of balancing efficacy with quality of life. Other mutations, such as KIT or NRAS, have fewer targeted options, making immunotherapy or enrollment in clinical trials important considerations.

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