Role of neoadjuvant pembrolizumab in advanced melanoma

Melanoma, a malignancy originating from melanocytes, poses a significant global health challenge, with approximately 325,000 cases and 57,000 deaths annually. Advanced melanoma (AM), categorized as stage III and IV, presents considerable treatment challenges due to its complex mutational landscape. Traditional treatment options have included checkpoint inhibitors and BRAF inhibitors, with pembrolizumab emerging as a promising agent. Approved by the FDA and EMA for various stages of melanoma, pembrolizumab is a humanized monoclonal antibody that blocks the PD-1/PD-L1 interaction, thereby enhancing immune system-mediated tumor eradication. This abstract discusses a recent phase 2 clinical trial evaluating the efficacy of neoadjuvant (presurgery) versus adjuvant (postsurgery) pembrolizumab treatment in resectable stage III or IV melanoma. The study, involving 313 patients across 90 US hospitals, found that neoadjuvant-adjuvant pembrolizumab significantly improved event-free survival (72%) compared to adjuvant-only treatment (49%) after 2 years. Treatment-related adverse events were consistent with known profiles, including fatigue, nausea, and diarrhea, without new severe adverse effects. No increase in surgery-related complications was observed with neoadjuvant treatment. These findings suggest that neoadjuvant pembrolizumab offers substantial benefits over adjuvant-only treatment, although further research is warranted. Future studies should focus on larger cohorts, diverse demographics, and extended follow-up to validate these results and potentially integrate neoadjuvant pembrolizumab into standard treatment protocols for advanced melanoma.