Pembrolizumab versus placebo as adjuvant therapy in resected stage IIB or IIC melanoma: Long-term follow-up, crossover, and rechallenge with pembrolizumab in the phase III Keynote-716 study
Abstract
Background:
Adjuvant pembrolizumab prolonged recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) in patients with resected stage IIB/IIC melanoma in KEYNOTE-716. Results of a post hoc 4-year analysis are reported, including progression/recurrence-free survival 2 (PRFS2).
Methods:
Patients were randomly assigned 1:1 to pembrolizumab 200 mg or placebo intravenously every 3 weeks (part 1). RFS was the primary end point; DMFS was secondary. Patients with recurrence following placebo or 17 cycles of pembrolizumab could cross over to or be rechallenged with pembrolizumab (part 2).
Results:
Median follow-up (n = 976) was 52.8 months (range, 39.4–64.8). RFS (HR, 0.62 [95 % CI, 0.50–0.78]) and DMFS (HR, 0.59 [0.45–0.77]) favored pembrolizumab. At 48 months, RFS rates were 71.3 % for pembrolizumab and 58.3 % for placebo, and DMFS rates were 81.0 % and 70.1 %, respectively. The HR for PRFS2 was 0.75 (95 % CI, 0.56–1.01); 48-month PRFS2 rates were 82.5 % for pembrolizumab and 76.7 % for placebo. In the crossover population, median follow-up was 36.9 months; median RFS was not reached (NR; 95 % CI, 16.8-NR; 48-month RFS, 50.6 %) in patients with resectable disease (n = 41) and median progression-free survival was 22.0 months (4.5-NR) in patients with unresectable disease (n = 30). Among patients rechallenged, median follow-up was 21.9 months; none with resectable disease had recurrence (n = 6) and 1 with unresectable disease had best response of stable disease (n = 3). No new safety signals were observed.
Conclusions:
With > 4 years follow-up, pembrolizumab continued to prolong RFS and DMFS and had antitumor activity in patients who crossed over to pembrolizumab. Trial registration: NCT03553836
Document Type
Journal Article
Volume
220
Funding Information
Merck Sharp & Dohme LLC
School
School of Medical and Health Sciences
Copyright
subscription content
Publisher
Elsevier
Comments
Luke, J. J., Ascierto, P. A., Khattak, M. A., Rutkowski, P., Del Vecchio, M., Spagnolo, F., ... & Long, G. V. (2025). Pembrolizumab versus placebo as adjuvant therapy in resected stage IIB or IIC melanoma: Long-term follow-up, crossover, and rechallenge with pembrolizumab in the phase III KEYNOTE-716 study. European Journal of Cancer, 220, Article 115381. https://doi.org/10.1016/j.ejca.2025.115381