The phase 3 NADINA trial studied patients with high-risk melanoma and compared two cycles of neoadjuvant ipilimumab plus nivolumab (given before surgery) with standard adjuvant nivolumab (given after surgery). The results showed that starting immunotherapy before surgery significantly improved event-free survival. At 24 months, 77.3% of patients in the neoadjuvant group were event-free, compared with 55.7% in the adjuvant group. Patients who had a major pathologic response after neoadjuvant treatment often did not need additional therapy, helping them avoid extra side effects.
There are still important treatment decisions to consider. Targeted therapy with BRAF and MEK inhibitors works well for patients with BRAF mutations, but it may not provide the same long-lasting immune control as immunotherapy. Adjuvant immunotherapy also carries about a 10% risk of serious immune-related side effects, and while it improves recurrence-free survival, it has not clearly been shown to extend overall survival. Patients with large, visible lymph node disease are now seen as strong candidates for neoadjuvant combination immunotherapy.
Researchers are also testing new approaches to further improve survival. These include PRAME-targeted T-cell therapies, personalized cancer vaccines combined with PD-1 inhibitors, T-cell engagers, and new oncolytic viruses. The main goal is to treat melanoma earlier and more effectively, preventing it from spreading to critical areas such as the brain and spine.