Adjuvant pembrolizumab in stage II melanoma: Outcomes by primary tumor location in the randomized, double-blind, phase III KEYNOTE-716 trial
Abstract
Background: Previous results from the KEYNOTE-716 trial demonstrated significantly improved recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) with adjuvant pembrolizumab versus placebo in patients with resected stage IIB or IIC melanoma. We present a post hoc analysis of efficacy according to primary tumor location. Methods: KEYNOTE-716 (NCT03553836) is a randomized, multicenter, double-blind, phase III study. Patients aged ≥ 12 years with newly diagnosed, resected stage IIB or IIC melanoma (sentinel node-negative) were randomly assigned (1:1) to pembrolizumab 200 mg every 3 weeks (2 mg/kg up to 200 mg for pediatric patients) or placebo. This post hoc analysis evaluated RFS and DMFS by primary tumor location of the head/neck, trunk, or extremities. Results: Overall, 976 patients were assigned to pembrolizumab (n = 487) or placebo (n = 489). Median follow-up was 39.4 months (range 26.0–51.4). The hazard ratios {HRs (95% confidence interval [CI])} for RFS were 0.60 (0.38–0.93) for the head/neck subgroup, 0.57 (0.38–0.84) for the trunk subgroup, and 0.69 (0.47–1.02) for the extremities subgroup. The HRs (95% CI) for DMFS were 0.65 (0.37–1.14) for the head/neck subgroup, 0.59 (0.38–0.92) for the trunk subgroup, and 0.53 (0.31–0.90) for the extremities subgroup. Conclusion: RFS and DMFS consistently favored adjuvant pembrolizumab over placebo in most subgroups analyzed in this post hoc analysis from the KEYNOTE-716 trial. These results support the benefit of adjuvant pembrolizumab on RFS and DMFS in patients with resected high-risk stage II melanoma, irrespective of primary tumor location.
Document Type
Journal Article
Date of Publication
1-1-2025
Funding Information
Merck Sharp & Dohme LLC / National Health and Medical Research Council of Australia
School
School of Medical and Health Sciences
Grant Number
NHMRC Number : APP2018514
Copyright
subscription content
Publisher
Springer
Recommended Citation
Yoon, C. H., Ross, M. I., Gastman, B. R., Luke, J. J., Ascierto, P. A., Long, G. V., Rutkowski, P., Khattak, M., Del Vecchio, M., de la Cruz Merino, L., Mackiewicz, J., Chiarion-Sileni, V., Schadendorf, D., Carlino, M. S., Zhao, Y., Fukunaga-Kalabis, M., Krepler, C., Eggermont, A. M., Gershenwald, J. E., & Sondak, V. K. (2025). Adjuvant pembrolizumab in stage II melanoma: Outcomes by primary tumor location in the randomized, double-blind, phase III KEYNOTE-716 trial. DOI: https://doi.org/10.1245/s10434-024-16642-6
Comments
Yoon, C. H., Ross, M. I., Gastman, B. R., Luke, J. J., Ascierto, P. A., Long, G. V., ... & Sondak, V. K. (2025). Adjuvant pembrolizumab in stage II melanoma: Outcomes by primary tumor location in the randomized, double-blind, phase III KEYNOTE-716 trial. Annals of Surgical Oncology, 32, 2756-2764. https://doi.org/10.1245/s10434-024-16642-6