malignant melanoma
Melanoma has been at the forefront of precision oncology and immunotherapy for over a decade. The discovery that approximately 50% of cutaneous melanomas harbor BRAF V600E/K mutations led to the development of BRAF/MEK inhibitor combinations (dabrafenib/trametinib, vemurafenib/cobimetinib), while the success of ipilimumab and nivolumab established immunotherapy as a curative-intent treatment for advanced disease, with long-term survival exceeding 20% at 10 years in some trials.
Current trials investigate anti-PD-1/LAG-3 combinations (relatlimab/nivolumab, already approved), triple checkpoint blockade, personalized neoantigen vaccines combined with anti-PD-1, tumor-infiltrating lymphocyte (TIL) therapy (lifileucel, FDA approved), and BRAF/MEK inhibitor combinations with immunotherapy for BRAF-mutated disease. Adjuvant trials aim to prevent recurrence in resected high-risk Stage III disease.
BRAF mutation status is required for enrollment in targeted therapy trials. Uveal, mucosal, and acral melanoma subtypes have distinct biology and are studied separately from cutaneous melanoma.