Precision oncology in advanced melanoma: molecular landscapes and personalized therapy recommendations from the Molecular Tumor Board Freiburg
A partir du profil multi-omique d'échantillons tumoraux provenant de 98 patients atteints d'un mélanome cutané ou de l'uvée de stade avancé, cette étude évalue l'intérêt clinique des profils moléculaires et des recommandations des réunions de concertation pluridisciplinaire pour personnaliser les traitements et améliorer les résultats thérapeutiques
Immune checkpoint inhibitors (ICIs) and BRAF/MEK kinase inhibitors have substantially improved survival in advanced melanoma; however, therapeutic resistance and severe toxicities underscore the ongoing need for alternative strategies. Here, we evaluate the clinical utility of multi-omic profiling, biomarker-stratified recommendations, and survival outcomes within a prospective cohort of 98 patients with advanced cutaneous or uveal melanoma evaluated by the Molecular Tumor Board Freiburg (MTB-FR) between 2021 and 2024. Completed profiling revealed at least one potential actionable target beyond classical BRAF V600 mutations in 83.8% of cases. Alterations in NRAS, atypical BRAF variants, CDK4/6 pathway amplifications, and DNA-damage response (DDR) gene mutations most frequently guided board recommendations. Biomarker-stratified therapies were recommended for 68.4% of patients, and personalized immunotherapy combinations for 72.4%. The treatment implementation rate was 33.8% (n = 27), achieving an overall disease control rate (DCR) of 42.9% and an overall response rate (ORR) of 10.7%. These findings demonstrate that comprehensive molecular profiling in a real-world setting uncovers actionable alterations, providing viable subsequent treatment avenues that may optimize outcomes for heavily pretreated melanoma patients beyond established standards of care. Ultimately, prospective, randomized, biomarker-driven trials remain essential to validate whether these individualized diagnostic strategies translate into a reproducible survival benefit.
npj Precision Oncology , article en libre accès, 2026