Neoadjuvant/adjuvant or adjuvant pembrolizumab in melanoma

A phase II study recently published on The New England Journal of Medicine showed that pembrolizumab given as both neoadjuvant and adjuvant therapy led to a significantly longer event-free survival than adjuvant-only pembrolizumab in patients with stage IIIB to IVC resectable melanoma, with adverse events similar between groups.

This phase II trial is the first in melanoma that directly compared a neoadjuvant–adjuvant with an adjuvant immunotherapy regimen. 313 patients with clinically detectable stage IIIB to IV melanoma amenable to surgical resection were randomized to receive three doses of neoadjuvant pembrolizumab, followed by surgery and adjuvant pembrolizumab, or upfront surgery followed by adjuvant pembrolizumab for a year; the interval from the last dose of neoadjuvant pem­brolizumab to surgery was expected to be 5 weeks or less. Median follow-up was 14.7 months; event-free survival at 2 years was 72% in the neoadjuvant-adjuvant group versus 49% in the adjuvant group, with no toxic effects identified. Data establish that strong consideration and preference should be given to neoadjuvant therapy for patients with surgically resectable stage III/IV melanoma and highlights the importance of a multidisciplinary approach with surgeons and oncologists to identify the candidates for this approach and to ensure that patients proceed with surgery in a timely fashion after neoadjuvant therapy. As authors conclude, «Among patients with resectable stage III or IV melanoma, event-free survival was significantly longer among those who received pembrolizumab both before and after surgery than among those who received adjuvant pembrolizumab alone». Further follow-up will determine whether this neoadjuvant approach in melanoma has an overall survival benefit over adjuvant therapy alone as well.