Neoadjuvant ipilimumab plus nivolumab in melanoma: five-year outcomes from the phase 2 PRADO trial

Neoadjuvant ipilimumab plus nivolumab has become the standard therapy for stage III melanoma, but long-term data are lacking. In the phase 2 PRADO trial, at the Netherlands Cancer Institute (Amsterdam), 99 patients with stage III macroscopic melanoma received this regimen. Five-year survival data from PRADO have now been published. Five-year event-free survival rate, relapse-free survival rate, distant metastasis-free survival rate, and overall survival rate were 71%, 74%, 79%, and 86%, respectively. Ongoing grade 1-2 immune-related adverse events occurred in 69% of patients alive, predominantly vitiligo and hypothyroidism. Major pathologic response, high tumor mutational burden, high interferon-gamma signature, and PD-L1 expression of 1% or higher were associated with favorable outcomes. Combined high TMB, IFNγ, and PD-L1 expression yielded 100% MPR and 100% 5-year EFS, whereas triple low expression had only 18% MPR and 41% 5-year EFS. The authors conclude that these findings demonstrate favorable long-term outcomes with neoadjuvant ipilimumab plus nivolumab for stage III melanoma in patients with an MPR, and identify IFNγ and PD-L1 as promising baseline biomarkers.