FDA Approves Cemiplimab as First, Only Adjuvant Immunotherapy for High-Risk CSCC

Cemiplimab (Libtayo; Regeneron Pharmaceuticals) has been approved as an adjuvant treatment for adult patients with cutaneous squamous cell carcinoma (CSCC) who are at high risk of recurrence after surgery and radiation.1

The therapy significantly extends disease-free survival (DFS) compared with placebo, with a 68% lower risk of disease recurrence or death, according to the results of the phase 3 C-POST trial (NCT03969004) that the FDA approval was based on.2

Vishal A. Patel, MD

"Patients whose CSCC is at a high risk of recurrence following surgery and radiation often have the poorest outcomes. Until now, we lacked options to help prevent a devastating recurrence and immunotherapy was only available for patients with advanced CSCC who were no longer candidates for curative surgery or curative radiation,” said Vishal A. Patel, MD, associate professor of dermatology and of medicine (hematology/oncology) at the George Washington (GW) University School of Medicine & Health Sciences, and director of the Cutaneous Oncology Program, GW Cancer Center. “Many patients who undergo surgical resection of their CSCC are later found, on full pathological evaluation, to be at high risk of recurrence.”

Cemiplimab is now the first and only immunotherapy approved in the adjuvant setting, representing a practice-changing opportunity for these patients, Patel added.

The C-POST trial included 415 patients at high risk of recurrence due to features such as extracapsular extension or having multiple lymph nodes affected. Patients were randomized in a 1:1 fashion to receive adjuvant cemiplimab (n = 209) or placebo (n = 206) for up to 48 weeks, with DFS as the primary end point. At a median follow-up of 24 months, the HR for recurrence or death was 0.32 (95% CI, 0.20-0.51; P < .0001) for those taking the medication compared with placebo.

The median duration of treatment was 47.9 weeks for cemiplimab and 47.7 weeks for placebo. At 24 months, the estimated DFS was 87.1% (95% CI, 80.3-91.6) for cemiplimab and 64.1% (95% CI, 55.9-71.1) for placebo. There were 65 events of disease recurrence or death in the placebo group and 24 events in the cemiplimab group.

The most common adverse events (AEs) with cemiplimab were fatigue (22.0%), pruritus (16.1%), rash (16.1%), and diarrhea (15.6%). In 9.8% of patients taking cemiplimab, AEs led to discontinuation of treatment compared with 1.5% receiving the placebo.

Research into cemiplimab in patients with metastatic CSCC had shown that cemiplimab produced responses in about half of patients, making it the standard of care in that setting and thus providing the basis for moving it into an earlier stage of treatment, Danny Rischin, MD, medical oncologist and codirector of the Division of Cancer Medicine at the Peter MacCallum Cancer Centre in Melbourne, Australia, explained in an interview with The American Journal of Managed Care®.3

In addition to being approved to treat CSCC, cemiplimab is also approved to treat basal cell carcinoma and non–small cell lung cancer either in combination with chemotherapy or alone in tumors without EGFR, ALK, or ROS1 mutations.

“CSCC is one of the most common skin cancers in the world, with an estimated 1.8 million cases diagnosed each year in the U.S. alone. While it can often be treated successfully with surgery and radiation, many patients face serious risk of advanced disease recurrences,” said Samantha R. Guild, president of the AIM at Skin Cancer Foundation.1 “This approval is wonderful news for people living with CSCC…”

References

1. Libtayo (cemiplimab-rwlc) approved in the U.S. as first and only immunotherapy for adjuvant treatment of cutaneous squamous cell carcinoma (CSCC) with a high risk of recurrence after surgery and radiation. News release. Regeneron. October 8, 2025. Accessed October 8, 2025. https://investor.regeneron.com/news-releases/news-release-details/libtayor-cemiplimab-rwlc-approved-us-first-and-only

2. Rischin D, Porceddu S, Day F, et al; C-POST Trial Investigators. Adjuvant cemiplimab or placebo in high-risk cutaneous squamous-cell carcinoma. N Engl J Med. 2025;393(8):774-785. doi:10.1056/NEJMoa2502449

3. Steinzor P, Rischin D. Spotlight: cemiplimab shows promising results in adjuvant treatment for cSCC. AJMC®. June 1, 2025. Accessed October 8, 2025. https://www.ajmc.com/view/spotlight-cemiplimab-shows-promising-results-in-adjuvant-treatment-for-cscc