Neoadjuvant cemiplimab and surgery for stage II-IV cutaneous squamous-cell carcinoma: follow-up and survival outcomes of a single-arm, multicentre, phase 2 study


Neil D. Gross, Department of Head and Neck Surgery, University of Texas MD Anderson Cancer Centre, Houston, TX, USA. Electronic address:
David M. Miller, Department of Medicine, Division of Hematology/Oncology, and Department of Dermatology, Massachusetts General Hospital, Boston, MA, USA.
Nikhil I. Khushalani, Department of Cutaneous Oncology, Moffitt Cancer Centre, Tampa, FL, USA.
Vasu Divi, Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, USA.
Emily S. Ruiz, Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Evan J. Lipson, Bloomberg-Kimmel Institute for Cancer Immunotherapy and Sidney Kimmel Comprehensive Cancer Centre at Johns Hopkins, Baltimore, MD, USA.
Friedegund Meier, Department of Dermatology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; Skin Cancer Center, University Cancer Centre Dresden and National Center for Tumor Diseases, Dresden, Germany.
Yungpo Bernard Su, Head and Neck Medical Oncology, Nebraska Cancer Specialists, Omaha, NE, USA.
Paul L. Swiecicki, Rogel Comprehensive Cancer Centre, University of Michigan, Ann Arbor, MI, USA.
Jennifer Atlas, Levine Cancer Institute, Atrium Health, Charlotte, NC, USA.
Jessica L. Geiger, Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA.
Axel Hauschild, Department of Dermatology, Schleswig-Holstein University Hospital, Kiel, Germany.
Jennifer H. Choe, Duke Cancer Institute, Durham, NC, USA.
Brett G. Hughes, Department of Cancer Care Services, Royal Brisbane and Women's Hospital and University of Queensland, Brisbane, QLD, Australia.
Dirk Schadendorf, Department of Dermatology, University Hospital of Essen and German Cancer Consortium, Partner Site Essen, Essen, Germany.
Vishal A. Patel, Departments of Dermatology, Medicine, and Oncology, George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
Jade Homsi, Harold C Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Janis M. Taube, Department of Dermatology, Johns Hopkins Hospital, Baltimore, MD, USA.
Annette M. Lim, Department of Medical Oncology, Peter MacCallum Cancer Centre and University of Melbourne, Melbourne, VIC, Australia.
Renata Ferrarotto, Department of Thoracic and Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Centre, Houston, TX, USA.
Suk-Young Yoo, Regeneron Pharmaceuticals, Tarrytown, NY, USA.
Melissa Mathias, Regeneron Pharmaceuticals, Tarrytown, NY, USA.
Hyunsil Han, Regeneron Pharmaceuticals, Tarrytown, NY, USA.
Frank Seebach, Regeneron Pharmaceuticals, Tarrytown, NY, USA.
Israel Lowy, Regeneron Pharmaceuticals, Tarrytown, NY, USA.
Matthew G. Fury, Regeneron Pharmaceuticals, Tarrytown, NY, USA.
Danny Rischin, Department of Medical Oncology, Peter MacCallum Cancer Centre and University of Melbourne, Melbourne, VIC, Australia.

Document Type

Journal Article

Publication Date



The Lancet. Oncology








BACKGROUND: We previously reported rates of pathological complete responses (51% [95% CI 39-62] per independent central review, the primary endpoint) and major pathological responses (13% per independent central review, a secondary endpoint) to neoadjuvant cemiplimab (an anti-PD-1 inhibitor) among 79 patients with locoregionally advanced, resectable cutaneous squamous cell carcinoma. Here, we present follow-up data, including event-free, disease-free, and overall survival. METHODS: This single-arm, multicentre, phase 2 study included patients aged 18 years or older with resectable stage II-IV (M0) cutaneous squamous cell carcinoma and Eastern Cooperative Oncology Group performance status of 0 or 1. Patients received up to four planned doses of neoadjuvant cemiplimab 350 mg intravenously every 3 weeks followed by curative-intent surgery. After surgery, per investigator discretion, patients received either adjuvant cemiplimab for up to 48 weeks, radiotherapy, or observation alone. Secondary endpoints included in this follow-up analysis are event-free survival, disease-free survival, and overall survival, all summarised using the Kaplan-Meier method. Activity and safety endpoints were analysed for all enrolled patients who received at least one dose of neoadjuvant cemiplimab. In this report, safety data are reported for all patients who received at least one dose of adjuvant cemiplimab. This trial is registered with, NCT04154943, has completed enrolment and follow-up is ongoing. FINDINGS: Between March 20, 2020, and July 8, 2021, 79 patients were enrolled. Median age was 73 years (IQR 66-81), 67 (85%) patients were male, 12 (15%) were female, 69 (87%) were White, one was Asian (1%), one was other race (1%), and race was not reported for eight (10%). As of data cutoff (Dec 1, 2022), median follow-up was 18·7 months (IQR 15·6-22·1) for all 79 patients. Among 70 patients who had surgery, 65 (93%) had post-surgical management data: 32 (49%) of 65 were observed postoperatively, 16 (25%) received adjuvant cemiplimab, and 17 (26%) received adjuvant radiotherapy. 11 (14%) of 79 patients had event-free survival events, with an estimated 12-month event-free survival of 89% (95% CI 79-94) for all patients. None of 40 patients who had a pathological complete response and one (10%) of ten patients with major pathological response had recurrence. Six (9%) of 70 patients who completed surgery had a disease-free survival event, with an estimated 12-month disease-free survival of 92% (95% CI 82-97). Nine (11%) of 79 patients died, with an estimated 12-month overall survival for all patients of 92% (95% CI 83-96). Four (25%) of 16 patients who received adjuvant cemiplimab treatment had grade 3 adverse events, including one (6%) who had increased blood potassium, one (6%) who had traumatic limb amputation, and two who had serious adverse events (one [6%] cardiomyopathy and one [6%] hypophysitis). There were no grade 4 adverse events or treatment-related deaths. INTERPRETATION: For patients with resectable stage II-IV cutaneous squamous cell carcinoma, neoadjuvant cemiplimab followed by surgery might be a potential treatment option, addressing a substantial unmet need. FUNDING: Regeneron Pharmaceuticals and Sanofi.