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

Author(s): Danny Rischin, M.D.^1,2; Sandro Porceddu, M.D.³; Fiona Day, Ph.D.⁴; Daniel P. Brungs, M.B., B.S., M.Med., Ph.D.^5,6; Hayden Christie, M.B., B.S.⁷; James E. Jackson, M.B., B.S., Ph.D.⁸; Brian N. Stein, M.D.⁹; Yungpo Bernard Su, M.D.¹⁰; Rahul Ladwa, M.B., Ch.B., M.Phil.¹¹; Gerard Adams, M.B., Ch.B.¹²; Samantha E. Bowyer, M.B., B.Ch.¹³; Zulfiquer Otty, M.B., B.S.¹⁴; Naoya Yamazaki, M.D., Ph.D.¹⁵; Paolo Bossi, M.D.^16,17; Amarnath Challapalli, Ph.D.¹⁸; Axel Hauschild, M.D., Ph.D.¹⁹; Annette M. Lim, Ph.D.^1,2; Vishal A. Patel, M.D.²⁰; Joanna L. Walker, M.D.²¹; Maite De Liz Vassen Schurmann, M.D.²²; Paola Queirolo, M.D.²³; Javier Cañueto, M.D., Ph.D.²⁴; Flavio Augusto Ferreira da Silva, M.D.²⁵; Alexander Stratigos, M.D.²⁶; Alexander Guminski, M.B., B.S., Ph.D.²⁷; Charles Lin, M.D.^28,29; Fernanda Damian, M.D.³⁰; Lukas Flatz, M.D.³¹; Anne E. Taylor, M.B., B.S.³²; David R. Carr, M.D.³³; Samuel Harris, M.B., B.S.³⁴; Dmitry Kirtbaya, M.D.³⁵; Gaëlle Quereux, M.D., Ph.D.³⁶; Piotr Rutkowski, M.D., Ph.D.³⁷; Nicole Basset-Seguin, M.D., Ph.D.³⁸; Nikhil I. Khushalani, M.D.³⁹; Caroline Robert, M.D., Ph.D.⁴⁰; Haisong Ju, M.D., Ph.D.⁴¹; Camryn Joseph, Pharm.D.⁴¹; Shikha Bansal, M.D.S.⁴¹; Chieh-I Chen, M.P.H.⁴¹; Frank Seebach, M.D., Ph.D.⁴¹; Suk-Young Yoo, Ph.D.⁴¹; Israel Lowy, M.D., Ph.D.⁴¹; Priscila Goncalves, M.D.⁴¹; Matthew G. Fury, M.D.⁴¹; for the C-POST Trial Investigators*;

Source: DOI: 10.1056/NEJMoa2502449

Dr. Anjan Patel's Thoughts

The C-POST trial investigated adjuvant cemiplimab vs placebo in high-risk cutaneous squamous cell carcinoma (CSCC) post-surgery and radiation, demonstrating significant improvement in disease-free survival (DFS) (24-month 87% vs 64%) with a 68% reduction in recurrence or death risk (HR 0.32). There were also reduced locoregional and distant recurrence rates. If approved, this would be the first drug in this indication, so keep an eye out for the FDA review.

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; 9% 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.)

Author Affiliations

¹Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia; ²Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia; ³Department of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia; ⁴Department of Medical Oncology, Calvary Mater Newcastle, Waratah, NSW, Australia; ⁵Illawarra Cancer Care Centre, Wollongong Hospital, Wollongong, NSW, Australia; ⁶Graduate School of Medicine, University of Wollongong, Wollongong, NSW, Australia; ⁷Cancer Care Centre Hervey Bay, Urraween, QLD, Australia; ⁸Radiation Oncology Centers, Gold Coast, QLD, Australia; ⁹Adelaide Cancer Centre, Adelaide, SA, Australia; ¹⁰Head and Neck Medical Oncology, Nebraska Cancer Specialists, Omaha; ¹¹Princess Alexandra Hospital, Woolloongabba, QLD, Australia; ¹²Radiation Oncology, Genesis Care, Bundaberg, QLD, Australia; ¹³Department of Medical Oncology, Sir Charles Gairdner Hospital, Perth, WA, Australia; ¹⁴Townsville Cancer Centre, Townsville University Hospital, Townsville, QLD, Australia; ¹⁵National Cancer Center Hospital, Tokyo; ¹⁶Department of Biomedical Sciences, Humanitas University, Milan; ¹⁷IRCCS Humanitas Research Hospital, Milan; ¹⁸Bristol Cancer Institute, University Hospitals Bristol and Weston NHS Foundation Trust, Bristol, United Kingdom; ¹⁹Department of Dermatology, University Hospital, Kiel, Germany; ²⁰George Washington University School of Medicine and Health Sciences, Washington, DC; ²¹Department of Dermatology, Hospital of the University of Pennsylvania, Philadelphia; ²²Animi Oncology Treatment Unit, University Planalto Catarinense, Lages, Brazil; ²³Melanoma and Sarcoma Division, European Institute of Oncology, IRCCS, Milan; ²⁴Department of Dermatology, Complejo Asistencial Universitario de Salamanca, Salamanca, Spain; ²⁵Department of Clinical Oncology, Hospital de Amor Barretos, São Paulo; ²⁶First Department of Dermatology–Venereology, University of Athens Medical School, Andreas Sygros Hospital, Athens; ²⁷Department of Medical Oncology, Royal North Shore Hospital, St. Leonards, NSW, Australia; ²⁸Department of Radiation Oncology, Royal Brisbane and Women’s Hospital, Herston, QLD, Australia; ²⁹School of Medicine, University of Queensland, Brisbane, Australia; ³⁰Centro de Pesquisa em Oncologia, Hospital São Lucas, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, Brazil; ³¹University Hospital Tübingen, Tübingen, Germany; ³²Central Adelaide Local Health Network, Royal Adelaide Hospital, Adelaide, SA, Australia; ³³Department of Dermatology, Ohio State University Medical Center, Columbus; ³⁴Bendigo Cancer Centre, Bendigo Health, Bendigo, VIC, Australia; ³⁵State Budgetary Institution of Healthcare, Oncology Dispensary No. 2, Ministry of Healthcare of Krasnodar Region, Sochi, Russia; ³⁶Dermatology Department, Nantes University, Centre Hospitalier Universitaire Nantes, Centre d’Investigation Clinique 1413, Immunologie et Nouveaux Concepts en Immunothérapie, Unité Mixte de Recherche 1302, Nantes, France; ³⁷Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland; ³⁸Hôpital Saint Louis, Assistance Publique–Hôpitaux de Paris, Paris; ³⁹Department of Cutaneous Oncology, Moffitt Cancer Center, Tampa, FL; ⁴⁰Department of Oncology, Gustave Roussy and Université Paris Saclay, Villejuif, France; ⁴¹Regeneron Pharmaceuticals, Tarrytown, NY;

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