Adjuvant Cemiplimab or Placebo in High-Risk Cutaneous Squamous-Cell Carcinoma

Danny Rischin, Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.
Sandro Porceddu, Department of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.
Fiona Day, Department of Medical Oncology, Calvary Mater Newcastle, Waratah, NSW, Australia.
Daniel P. Brungs, Illawarra Cancer Care Centre, Wollongong Hospital, Wollongong, NSW, Australia.
Hayden Christie, Cancer Care Centre Hervey Bay, Urraween, QLD, Australia.
James E. Jackson, Radiation Oncology Centers, Gold Coast, QLD, Australia.
Brian N. Stein, Adelaide Cancer Centre, Adelaide, SA, Australia.
Yungpo Bernard Su, Head and Neck Medical Oncology, Nebraska Cancer Specialists, Omaha.
Rahul Ladwa, Princess Alexandra Hospital, Woolloongabba, QLD, Australia.
Gerard Adams, Radiation Oncology, Genesis Care, Bundaberg, QLD, Australia.
Samantha E. Bowyer, Department of Medical Oncology, Sir Charles Gairdner Hospital, Perth, WA, Australia.
Zulfiquer Otty, Townsville Cancer Centre, Townsville University Hospital, Townsville, QLD, Australia.
Naoya Yamazaki, National Cancer Center Hospital, Tokyo.
Paolo Bossi, Department of Biomedical Sciences, Humanitas University, Milan.
Amarnath Challapalli, Bristol Cancer Institute, University Hospitals Bristol and Weston NHS Foundation Trust, Bristol, United Kingdom.
Axel Hauschild, Department of Dermatology, University Hospital, Kiel, Germany.
Annette M. Lim, Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.
Vishal A. Patel, George Washington University School of Medicine and Health Sciences, Washington, DC.
Joanna L. Walker, Department of Dermatology, Hospital of the University of Pennsylvania, Philadelphia.
Maite De Liz Vassen Schurmann, Animi Oncology Treatment Unit, University Planalto Catarinense, Lages, Brazil.
Paola Queirolo, Melanoma and Sarcoma Division, European Institute of Oncology, IRCCS, Milan.
Javier Cañueto, Department of Dermatology, Complejo Asistencial Universitario de Salamanca, Salamanca, Spain.
Flavio Augusto Ferreira da Silva, Department of Clinical Oncology, Hospital de Amor Barretos, São Paulo.
Alexander Stratigos, First Department of Dermatology-Venereology, University of Athens Medical School, Andreas Sygros Hospital, Athens.
Alexander Guminski, Department of Medical Oncology, Royal North Shore Hospital, St. Leonards, NSW, Australia.
Charles Lin, Department of Radiation Oncology, Royal Brisbane and Women's Hospital, Herston, QLD, Australia.
Fernanda Damian, Centro de Pesquisa em Oncologia, Hospital São Lucas, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, Brazil.
Lukas Flatz, University Hospital Tübingen, Tübingen, Germany.
Anne E. Taylor, Central Adelaide Local Health Network, Royal Adelaide Hospital, Adelaide, SA, Australia.
David R. Carr, Department of Dermatology, Ohio State University Medical Center, Columbus.
Samuel Harris, Bendigo Cancer Centre, Bendigo Health, Bendigo, VIC, Australia.
Dmitry Kirtbaya, State Budgetary Institution of Healthcare, Oncology Dispensary No. 2, Ministry of Healthcare of Krasnodar Region, Sochi, Russia.

Document Type

Journal Article

Publication Date

8-21-2025

Journal

The New England journal of medicine

Volume

393

Issue

8

DOI

10.1056/NEJMoa2502449

Abstract

BACKGROUND: Patients who have cutaneous squamous-cell carcinoma with high-risk features are at risk for recurrence after definitive local therapy. The benefit of systemic adjuvant therapy options has not been well established in clinical trials. METHODS: In a phase 3, randomized trial, we enrolled patients with local or regional cutaneous squamous-cell carcinoma, after surgical resection and postoperative radiotherapy, at high risk for recurrence owing to nodal features (extracapsular extension with largest node ≥20 mm in diameter or at least three involved nodes) or nonnodal features (in-transit metastases, T4 lesion [with bone invasion], perineural invasion, or locally recurrent tumor with ≥1 additional risk feature). Patients were assigned in a 1:1 ratio to receive adjuvant cemiplimab (350 mg) or placebo, administered intravenously every 3 weeks for 12 weeks, followed by a dose increase to 700 mg administered every 6 weeks for up to 36 weeks (≤48 weeks total). The primary end point was disease-free survival. Secondary end points included freedom from locoregional recurrence, freedom from distant recurrence, and safety. RESULTS: A total of 415 patients were assigned to cemiplimab (209) or placebo (206). The median follow-up was 24 months. Cemiplimab was superior to placebo with respect to disease-free survival (24 vs. 65 events; hazard ratio for disease recurrence or death, 0.32; 95% confidence interval [CI], 0.20 to 0.51; P<0.001). The estimated 24-month disease-free survival was 87.1% (95% CI, 80.3 to 91.6) with cemiplimab and 64.1% (95% CI, 55.9 to 71.1) with placebo. Cemiplimab led to lower risks of locoregional recurrence (9 events, vs. 40 with placebo; hazard ratio, 0.20; 95% CI, 0.09 to 0.40) and distant recurrence (10 vs. 26 events; hazard ratio, 0.35; 95% CI, 0.17 to 0.72). Adverse events of grade 3 or higher occurred in 23.9% of the patients who received cemiplimab and in 14.2% of those who received placebo; discontinuation due to adverse events occurred in 9.8% and 1.5%, respectively. CONCLUSIONS: Adjuvant cemiplimab therapy led to longer disease-free survival than placebo among patients at high risk for recurrence of cutaneous squamous-cell carcinoma. (Funded by Regeneron Pharmaceuticals and Sanofi; C-POST ClinicalTrials.gov number, NCT03969004.).

Department

Dermatology

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