Multinational phase 3 trial of neoadjuvant nivolumab and ipilimumab in resectable stage III melanoma

The multinational phase 3 NADINA trial compared neoadjuvant versus adjuvant immunotherapy for resectable macroscopic stage III melanoma. Patients were randomized to two cycles of neoadjuvant ipilimumab plus nivolumab followed by surgery with adjuvant therapy only for patients having partial response or nonrespons (neoadjuvant group) or to surgery followed by 12 cycles of adjuvant nivolumab (adjuvant group). At a median follow-up of 9.9 months, the 12-month event-free survival rate was 83.7% in the neoadjuvant group versus 57.2% in the adjuvant group (p<0.001). In the neoadjuvant group, 59.0% of patients had a major pathologic response, 8.0% had a partial response, 26.4% had a nonresponse, and 2.4% had progression; in 4.2% surgery had not yet been performed or was omitted. In the neoadjuvant group, 12-month recurrence-free survival rate was 95.1% among patients who had a major pathological response, 76.1% among those who had a partial response, and 57.0% among those who had a nonresponse. Systemic treatment-related adverse events of grade 3 or higher occurred in 29.7% of the patients in the neoadjuvant group and in 14.7% in the adjuvant group. The authors conclude that in this patient population, neoadjuvant nivolumab plus ipilimumab followed by surgery and response-drive adjuvant therapy resulted in longer event-free survival than surgery followed by adjuvant nivolumab.