• Neil D Gross, David M Miller, Nikhil I Khushalani, Vasu Divi, Emily S Ruiz, Evan J Lipson, Friedegund Meier, Yungpo B Su, Paul L Swiecicki, Jennifer Atlas, Jessica L Geiger, Axel Hauschild, Jennifer H Choe, Brett G M Hughes, Dirk Schadendorf, Vishal A Patel, Jade Homsi, Janis M Taube, Annette M Lim, Renata Ferrarotto, Howard L Kaufman, Frank Seebach, Israel Lowy, Suk-Young Yoo, Melissa Mathias, Keilah Fenech, Hyunsil Han, Matthew G Fury, and Danny Rischin.
• From the Department of Head and Neck Surgery (N.D.G.) and the Department of Thoracic and Head and Neck Medical Oncology (R.F.), M.D. Anderson Cancer Center, Houston, and the Harold C. Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas (J.H.); the Department of Medicine, Division of Hematology and Oncology (D.M.M.), the Department of Dermatology (D.M.M.), and the Department of Surgery (H.L.K.), Massachusetts General Hospital and Harvard Medical School, and the Department of Dermatology, Brigham and Women's Hospital and Harvard Medical School (E.S.R.) - all in Boston; the Department of Cutaneous Oncology, Moffitt Cancer Center, Tampa, FL (N.I.K.); the Department of Otolaryngology-Head and Neck Surgery, Stanford Cancer Institute, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA (V.D.); Bloomberg-Kimmel Institute for Cancer Immunotherapy and Sidney Kimmel Comprehensive Cancer Center (E.J.L., J.M.T.) and the Department of Dermatology, School of Medicine (J.M.T.), Johns Hopkins University, Baltimore; the Skin Cancer Center at the University Cancer Center and the National Center for Tumor Diseases Dresden, Department of Dermatology, University Hospital Carl Gustav Carus and Technische Universität Dresden, Dresden (F.M.), the Department of Dermatology, Schleswig-Holstein University Hospital, Kiel (A.H.), and the Department of Dermatology, University Hospital of Essen and German Cancer Consortium, Partner Site Essen, Essen (D.S.) - all in Germany; Head and Neck Medical Oncology, Nebraska Cancer Specialists, Omaha (Y.B.S.); Rogel Comprehensive Cancer Center, University of Michigan, Ann Arbor (P.L.S.); Levine Cancer Institute, Atrium Health, Charlotte (J.A.), and Duke Cancer Institute, Durham (J.H.C.) - both in North Carolina; Taussig Cancer Institute, Department of Hematology and Medical Oncology, Cleveland Clinic, Cleveland (J.L.G.); the Department of Cancer Care Services, Royal Brisbane and Women's Hospital and University of Queensland, Brisbane (B.G.M.H.), and the Department of Medical Oncology, Peter MacCallum Cancer Centre and University of Melbourne, Melbourne, VIC (A.M.L., D.R.) - both in Australia; the Departments of Dermatology, Medicine, and Oncology, George Washington University School of Medicine and Health Sciences, Washington, DC (V.A.P.); and Regeneron Pharmaceuticals, Tarrytown, NY (F.S., I.L., S.-Y.Y., M.M., K.F., H.H., M.G.F.).
• N. Engl. J. Med. 2022 Oct 27; 387 (17): 155715681557-1568.

BackgroundIn a pilot study involving patients with cutaneous squamous-cell carcinoma, a high percentage of patients had a pathological complete response with the use of two doses of neoadjuvant cemiplimab before surgery. Data from a phase 2 study are needed to confirm these findings.MethodsWe conducted a phase 2, confirmatory, multicenter, nonrandomized study to evaluate cemiplimab as neoadjuvant therapy in patients with resectable stage II, III, or IV (M0) cutaneous squamous-cell carcinoma. Patients received cemiplimab, administered at a dose of 350 mg every 3 weeks for up to four doses, before undergoing surgery with curative intent. The primary end point was a pathological complete response (the absence of viable tumor cells in the surgical specimen) on independent review at a central laboratory, with a null hypothesis that a pathological complete response would be observed in 25% of patients. Key secondary end points included a pathological major response (the presence of viable tumor cells that constitute ≤10% of the surgical specimen) on independent review, a pathological complete response and a pathological major response on investigator assessment at a local laboratory, an objective response on imaging, and adverse events.ResultsA total of 79 patients were enrolled and received neoadjuvant cemiplimab. On independent review, a pathological complete response was observed in 40 patients (51%; 95% confidence interval [CI], 39 to 62) and a pathological major response in 10 patients (13%; 95% CI, 6 to 22). These results were consistent with the pathological responses determined on investigator assessment. An objective response on imaging was observed in 54 patients (68%; 95% CI, 57 to 78). Adverse events of any grade that occurred during the study period, regardless of whether they were attributed to the study treatment, were observed in 69 patients (87%). Grade 3 or higher adverse events that occurred during the study period were observed in 14 patients (18%).ConclusionsNeoadjuvant therapy with cemiplimab was associated with a pathological complete response in a high percentage of patients with resectable cutaneous squamous-cell carcinoma. (Funded by Regeneron Pharmaceuticals and Sanofi; ClinicalTrials.gov number, NCT04154943.).Copyright © 2022 Massachusetts Medical Society.

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