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FDA approves adjuvant cemiplimab for high-risk cutaneous squamous cell carcinoma

On October 8, 2025, the U.S. Food and Drug Administration (FDA) approved adjuvant cemiplimab, a PD-1 inhibitor, for post-surgical high-risk cutaneous squamous cell carcinoma (CSCC).1 CSCC accounts for approximately one in five of all skin cancers and carries a known risk of recurrence and progression, particularly in patients with high-risk features. Whilst cemiplimab has already been approved for metastatic or locally advanced CSCC, no systemic therapy has been approved in the post-surgical, adjuvant setting for patients at high risk.2, 3

The FDA approval was based on findings from the Phase III C-POST trial (NCT03969004), which recruited 415 patients with high-risk features (including nodal involvement or aggressive local disease), who received surgery and post-operative radiation therapy. Patients were randomized 1:1 to either cemiplimab or placebo for up to 48 weeks. The primary endpoint of disease-free survival (DFS) was met, with a 24-month cut-off, where the cemiplimab and placebo arms had DFS rates of 87.1% (95% CI: 80.3–91.6) and 64.1% (95% CI: 55.9–71.1), respectively. The safety profile was consistent with prior experience; grade ≥3 events occurred in 23.9% versus 14.2% of patients receiving cemiplimab and placebo, respectively, and treatment discontinuation due to adverse events was 9.8% versus 1.5%.4

We spoke with Danny Rischin, MD, Peter MacCallum Cancer Centre, Melbourne, Australia, who discusses the significance of the trial data and the subsequent approval, stating that

“In terms of efficacy there was a marked improvement in disease-free survival that was statistically significant and clinically meaningful, and it’s the first systemic adjuvant treatment to improve outcomes for patients with high-risk, locally, radically advanced, cutaneous squamous cell carcinoma, and is likely to represent a potential new standard of care for these patients.”

For the first time, systemic adjuvant therapy has demonstrated a statistically and clinically meaningful benefit in preventing recurrence in patients with resected high-risk CSCC. This approach may allow clinicians to intervene earlier in disease evolution and reduce reliance on repeated salvage therapies or aggressive interventions when recurrence emerges. As longer-term and survival data mature, this approval may redefine standards of care in a patient population that has previously lacked validated postoperative systemic options.

References:

  1. Center for Drug Evaluation and Research. FDA approves cemiplimab-rwlc [Internet]. U.S. Food and Drug Administration. 2025 [cited 2025 Oct 9]. Available from: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-cemiplimab-rwlc-adjuvant-treatment-cutaneous-squamous-cell-carcinoma
  2. Dessinioti C, Stratigos AJ. Recent Advances in the Diagnosis and Management of High-Risk Cutaneous Squamous Cell Carcinoma. Cancers. 2022 Jul 21;14(14):3556.
  3. Center for Drug Evaluation and Research. FDA approves cemiplimab-rwlc for metastatic or locally advanced cutaneous squamous cell carcinoma. FDA [Internet]. 2019 Dec 20; [cited 2025 Oct 6]. Available from: https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-cemiplimab-rwlc-metastatic-or-locally-advanced-cutaneous-squamous-cell-carcinoma
  4. Rischin D, Porceddu SV, Day F, Brungs D, Christie HR, Jackson JE, et al. Phase 3 trial of adjuvant cemiplimab (cemi) versus placebo (pbo) for high-risk cutaneous squamous cell carcinoma (CSCC). Journal of Clinical Oncology. 2025 May 28;43(16_suppl):6001–1.

Written by Henry Shippey

Edited by Calum Lang