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.
Keywords
Adjuvant, Adjuvant therapy, Immune checkpoint inhibitors, Melanoma, Pembrolizumab, Skin neoplasms, Surgery
Document Type
Journal Article
Date of Publication
1-1-2025
Publication Title
Annals of Surgical Oncology
Publisher
Springer
School
School of Medical and Health Sciences
Funding Information
Funding for this study was provided by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. The funder contributed to study design, data collection, data analysis, and data interpretation in collaboration with the authors, and provided financial support for editorial and writing assistance. All authors had full access to the data and were involved in reviewing and editing the manuscript, approved the submitted draft, and vouch for the accuracy of the data reported. The corresponding author had the final responsibility to submit the manuscript for publication. RAS was supported by a National Health and Medical Research Council of Australia (NHMRC) investigator grant (APP2018514).
Funding received from the National Health and Medical Research Council (NHMRC)
APP2018514
Copyright
subscription content
Content Type
Metadata only
Recommended Citation
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
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