Neoadjuvant Cemiplimab in Patients With Stage II to IV Cutaneous Squamous Cell Carcinoma

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In an international, multicenter phase II clinical trial, 63.3% of patients with stage II to IV cutaneous squamous cell carcinoma saw their tumors nearly or completely eradicated when treated with the anti–PD-1 agent cemiplimab-rwlc before surgery. The results were presented by Gross et al at the European Society for Medical Oncology (ESMO) Congress 2022 (Abstract 7890) and were simultaneously published in The New England Journal of Medicine.

The immunotherapy cemiplimab was well tolerated, and the study met its primary endpoint with a pathologic complete response rate of 50.6%, meaning no tumor cells were found at surgery. Another 12.7% of patients had a major pathologic response, with less than 10% viable tumor found at surgery. The responses were confirmed by independent central pathologic review.

“These results represent the highest response rate to neoadjuvant anti–PD-1 monotherapy in any solid cancer so far and likely are the start of a practice change for how we treat advanced resectable cutaneous squamous cell carcinoma,” said study principal investigator and lead author Neil Gross, MD, Professor of Head and Neck Surgery at The University of Texas MD Anderson Cancer Center. “I’m excited to see how this new treatment approach impacts outcomes, including quality of life, as we continue long-term follow-up.”

More About Cutaneous Squamous Cell Carcinoma

About 1 million people in the United States are diagnosed with cutaneous squamous cell carcinoma each year, making it one of the most common forms of cancer. Most cases are easily treated by a dermatologist or primary care physician and do not require advanced care. However, most cutaneous squamous cell carcinomas occur in the head and neck regions—areas that receive heavy sun exposure—and, in the rare instances that they do grow and spread aggressively, they can affect the eyes, ears, nose, and mouth. The current standard of care, involving surgical excision and radiation, can be disfiguring and result in loss of important functions. Although not an endpoint of the study, the response to neoadjuvant immunotherapy enabled less invasive, function-preserving surgery in some cases.

In 2018, the U.S. Food and Drug Administration (FDA) approved cemiplimab for patients with metastatic cutaneous squamous cell carcinoma who are not candidates for curative surgery or radiation. The drug was first studied in the neoadjuvant setting for operable disease in a single-institution phase II study at MD Anderson that Dr. Gross designed and led. The results were presented at the ESMO Congress 2019 and published in Clinical Cancer Research in 2021. The 75% pathologic response rate from 20 patients in that study prompted this international, multicenter study ( identifier NCT04154943) to confirm the drug’s efficacy. 

Current Study

The single-arm study enrolled 79 patients in the United States, Australia, and Europe with operable stage II to IV cutaneous squamous cell carcinoma to receive four doses of neoadjuvant cemiplimab followed by curative-intent surgery, with optional adjuvant radiation therapy. Patients had scans before surgery, but the imaging responses (6.3% complete response) underestimated pathologic complete response (50.6%). The overall response rate from imaging was 68.4%, with most responses classified as partial responses.

A total of 67 patients (84.8%) were male, and the median age was 73. Consistent with cutaneous squamous cell carcinoma incidence, 87.3% of patients were White, and the head and neck region was the primary cancer site for 91.9% of patients.

Sixty-two patients received all four doses of therapy, and 70 patients underwent surgery. Of the nine patients who did not have surgery, three declined because imaging showed their cancer responded to the immunotherapy, two were lost to follow-up/noncompliance, two had progressive disease, and two experienced adverse events.

Overall, 14 patients (17.7%) experienced grade 3 or worse adverse events. The most common events of any grade were fatigue (30.4%), rash (13.9%), diarrhea (13.9%), and nausea (13.9%). Four patients died; one death, an exacerbation of cardiac failure, was considered related to treatment. There were no new safety signals for anti–PD-1 immunotherapy.

The research team will continue to follow the study participants and to report survival data and other outcomes when follow-up is complete. In the future, investigators hope to address still-unanswered questions about the optimal number of doses before surgery, which patients can safely avoid radiation and/or surgery, and how to predict which patients are most likely to respond to immunotherapy.

“I think where it's really going to make a huge difference is quality of life,” Dr. Gross said. “If you can avoid radiation or have a smaller surgery, and you can keep your eye, ear, or nose, that’s a huge win for people. That’s the excitement of this approach: the chance to make life so much better for our patients in the future.”

Disclosure: The study was funded by Regeneron Pharmaceuticals, Inc, and Sanofi. For full disclosures of the study authors, visit


The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.