Neoadjuvant ipilimumab plus nivolumab in melanoma

Five-years data from the PRADO trial, recently published on Nature Medicine, show benefits on event-free survival, relapse-free survival and overall survival with neoadjuvant ipilimumab and nivolumab in patients with stage III macroscopic melanoma.

The new study is reporting the 5-year update of the PRADO trial including survival, long-term toxicity and the first biomarker analyses; PRADO trial was the first trial in melanoma prospectively testing a surgical de-escalation approach and early data have shown that neoadjuvant ipilimumab plus nivolumab induced a pathologic response rate of 71%. These updated results demonstrate on 99 patients that this combination leads to a 71% event-free survival, 74% relapse-free survival, 79% distant metastasis-free survival and 86% overall survival. Major pathologic response, high tumor mutational burden, high IFNγ signature and PD-L1 expression of 1% or higher were associated with favorable outcomes. Combined high tumor mutational burden, IFNγ signature and PD-L1 expression yielded 100% major pathologic response and 100% 5-year event-free survival, whereas triple low expression had only 18% major pethologic response and 41% event-free survival. As authors conclude «This survival update of PRADO shows promising  long-term survival outcomes for patients treated with neoadjuvant ipilimumab and nivolumab, especially in patients who achieve a major pathologic response in the largest lymph node metastasis at baseline (index limph node). For patients without major pathologic response, alternative neoadjuvant and adjuvant schemes are needed. Baseline biomarkers such as IFNγ signature and PD-L1 expression might be promising biomarkers that could help identify these patients for escalation of therapy. Our findings support the potential for biomarker-guided personalization and response-adapted tailoring of surgical and adjuvant treatment strategies in the future».