Neoadjuvant Treatment Takes Center Stage for Patients with Resectable Melanoma

For patients with stage III melanoma, the goal is cure, but the risk for relapse is high. The standard approach has been complete surgical resection followed by adjuvant therapy — commonly, anti-PD-1 checkpoint-blocking antibodies (nivolumab and pembrolizumab) — to reduce the risk for recurrent disease by eliminating micrometastases. Early clinical data suggest that presurgical (i.e., neoadjuvant) treatment might yield better outcomes. In the industry-supported NADINA trial, the first randomized, phase 3 study testing this concept, researchers compared outcomes of 423 patients assigned either to two doses of neoadjuvant treatment (nivolumab plus ipilimumab) before surgery or to surgery upfront followed by adjuvant nivolumab alone (≤12 cycles).

Patients in the neoadjuvant arm who had a major pathologic response (59%) were given no further systemic therapy; those who had a pathologic partial response (8%) or nonresponse (26%) received adjuvant nivolumab or combination dabrafenib/trametinib. Estimated 12-month event-free survival was significantly superior in the neoadjuvant arm, compared with the adjuvant arm (84% vs. 57%). The neoadjuvant regimen was associated with a higher rate of systemic-treatment–related grade ≥3 adverse events (30% vs. 15% in the adjuvant arm).