Neoadjuvant or perioperative immunotherapy for resectable melanoma: The need for biomarkers

Groundbreaking studies have reshaped the treatment landscape for patients with resectable stage ≥IIIB melanoma by demonstrating the benefits of neoadjuvant therapy. Data from the NADINA and SWOG S1801 trials reveal substantial improvements in event-free survival compared to adjuvant therapy alone. These studies employed distinct neoadjuvant immunotherapy approaches - ipilimumab plus nivolumab in NADINA and anti-PD-1 monotherapy in SWOG S1801 - highlighting potential differences in efficacy and toxicity. The integration of biomarkers may improve the risk/benefit ratio by enabling personalized treatment selection between ipilimumab plus nivolumab versus anti-PD-1 monotherapy. In metastatic melanoma, molecular biomarkers such as BRAF mutational status and intratumoral PD-L1 expression can help guide treatment decisions; however, their, and other biomarkers', role in the neoadjuvant context has yet to be fully investigated. This commentary underscores the need to investigate whether these molecular markers, along with other biomarkers and clinical parameters, can inform neoadjuvant therapy in resectable stage ≥IIIB melanoma. We propose a coordinated effort involving retrospective analyses of current trials and prospective clinical studies, to define the role of biomarkers. A biomarker-guided approach could optimize efficacy and reduce toxicity, offering personalized treatment options for patients with resectable melanoma. As implementation of neoadjuvant therapy rapidly gains global adoption, we advocate for robust research to ensure that each patient receives the most effective and least toxic therapeutic option.