Neoadjuvant systemic therapy in stage III and IV resectable melanoma: an update to management and future directions

AIM: This article aims to review the role of neoadjuvant systemic therapy (NAST) in the management of clinical stage III or IV resectable melanoma. The review focusses on the evidence behind neoadjuvant systemic therapies and on developing a protocol for widespread implementation within the New Zealand health system. We outline suggested future directions for this evolving treatment. METHODS: A detailed literature review was conducted, examining the rationale, mechanisms of action and recent clinical trial data supporting the use of NAST in melanoma management. RESULTS: NAST provides notable immunological advantages by harnessing tumour antigen presence in situ, enhancing immune response and improving event-free survival (EFS) rates. Recent randomised phase II and III controlled trials have demonstrated significant improvements in EFS rates with NAST compared to standard adjuvant therapy alone. The SWOG-S1801 trial reported a 2-year EFS rate of 72% with neoadjuvant-adjuvant pembrolizumab compared to 49% for adjuvant-only therapy. The NADINA trial found a remarkable increase in 1-year EFS with neoadjuvant ipilimumab and nivolumab (83.7%) compared to adjuvant nivolumab alone (57.2%). CONCLUSION: Current evidence strongly supports incorporating NAST into standard clinical practice for resectable clinical stage III and IV melanoma, promising substantial improvements in patient outcomes with acceptable safety profiles.