The randomized phase III C-POST trial attempted to learn whether the standard-of-care treatment in advanced cutaneous squamous cell carcinoma—cemiplimab-rwlc, which blocks the PD-1/PD-L1 pathway—could reduce recurrence after definitive local therapy for patients who had high-risk features. According to the lead investigator of the study, Danny Rischin, MD, FAHMS, a medical oncologist at the Peter MacCallum Cancer Centre, Melbourne, Australia, adjuvant therapy with cemiplimab demonstrated “a statistically significant reduction in disease recurrence” in this patient population. These findings were presented at the 2025 ASCO Annual Meeting1 and simultaneously published in The New England Journal of Medicine.2
“While surgery and radiotherapy remain the cornerstone of treatment for high-risk cutaneous squamous cell carcinoma, there is a critical unmet need for systemic therapies to help prevent relapse and metastasis to ultimately drive better outcomes for patients,” stated Dr. Rischin in a statement. “The phase III C-POST trial demonstrates that cemiplimab is a highly active therapy in high-risk cutaneous squamous cell carcinoma, with clinically meaningful outcomes across primary and secondary endpoints and exceptionally low rates of locoregional and distant recurrence.”
Study Details
From June 2019 to August 2024, a total of 415 patients with local or regional cutaneous squamous cell carcinoma were enrolled in the C-POST trial after surgical resection and postoperative radiotherapy. The median patient age was 71 years (range, 33–95 years), and 84% were male. The high-risk criteria for recurrence included nodal features (extracapsular extension with largest node ≥ 20 mm in diameter or at least three involved nodes) or non-nodal features (in-transit metastases, T4 lesion [with bone invasion], perineural invasion, or locally recurrent tumor with at least one additional risk feature). A total of 83% had a head and neck primary; 58% had high-risk nodal features, and 42% had non-nodal features.
“The phase III C-POST trial demonstrates that cemiplimab is a highly active therapy in high-risk cutaneous squamous cell carcinoma....”— DANNY RISCHIN, MD, FAHMS
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Approximately half of the patients (n = 209) were assigned to receive 350 mg of adjuvant cemiplimab, and the other patients (n = 206) were assigned to receive placebo. Both were administered intravenously every 3 weeks for 12 weeks, followed by a dose increase of cemiplimab to 700 mg, which was given every 6 weeks for up to 36 weeks (≤ 28 weeks total). Crossover was permitted after disease recurrence.
The primary study endpoint was disease-free survival. Secondary study endpoints included freedom from locoregional recurrence, freedom from distant recurrence, overall survival, and safety. For the prespecified interim analysis 1, data cutoff (~50% of final disease-free survival events) was October 2024.
Key Results and Safety
The median follow-up was 24 months (range, 2–64 months). The investigators reported superior disease-free survival with cemiplimab vs placebo, with a hazard ratio (HR) of 0.32 (95% CI = 0.20–0.51; P < .0001). The estimated 24-month disease-free survival rate was 87% (95% CI = 80%–92%) with cemiplimab vs 64% (95% CI = 56%–71%) with placebo. Compared with placebo, use of cemiplimab improved both freedom from local-regional recurrence (HR = 0.20; 95% CI = 0.09–0.40) and freedom from distance recurrence (HR = 0.35; 95% CI = 0.17–0.72). The 24-month freedom from local-regional recurrence rate was 94.6% with cemiplimab vs 76.7% with placebo. The 24-month freedom from distance recurrence rate was 94.3% with cemiplimab vs 83.8% with placebo. As for overall survival, the most recent analysis (with an April 7, 2025, data cutoff) showed the hazard ratio for cemiplimab vs placebo was 0.78 (95% CI = 0.39–1.56).
As for safety, the investigators reported that 23.9% of those given cemiplimab and 14.2% of those given placebo had grade ≥ 3 treatment-emergent adverse events. The rate of treatment discontinuation as a result of treatment-emergent adverse events was 9.8% with cemiplimab and 1.5% with placebo.
Furthermore, the investigators performed exploratory analyses. They found disease-free survival benefits in patients with tumoral PD-L1 expression ≥ 1% (HR = 0.28; 95% CI = 0.15–0.52; n = 309) and < 1% (HR = 0.32; 95% CI = 0.12–0.86; n = 85).
DISCLOSURE: The study was sponsored by Regeneron Pharmaceuticals and Sanofi. Dr. Rischin has received institutional research funding from ALX Oncology, AstraZeneca, Bicara Therapeutics, Decibel Therapeutics, Erasca, Merck, and Regeneron; and reported an uncompensated relationship with Eisai, GlaxoSmithKline, Merck, Bicara Therapeutics, and Regeneron. For full disclosures of the other study authors, visit coi.asco.org.
REFERENCES
- Rischin D, Porceddu SV, Day F, et al: Phase 3 trial of adjuvant cemiplimab versus placebo for high-risk cutaneous squamous cell carcinoma. 2025 ASCO Annual Meeting. Abstract 6001. Presented May 31, 2025.
- Rischin D, Porceddu S, Day F, et al: Adjuvant cemiplimab or placebo in high-risk cutaneous squamous-cell carcinoma. N Engl J Med. May 31, 2025 (early release online).
Expert Point of View
Discussant of the abstract on the C-POST trial, Kevin Joseph Harrington, MBBS, PhD, Professor of Biological Cancer Therapies at the Institute of Cancer Research and a consultant clinical oncologist at The Royal Marsden NHS Foundation in London, shared these comments on the clinical implications of these findings.
“The C-POST trial should be considered as an important contribution to our understanding of how best to manage patients with high-risk cutaneous squamous cell cancers,” he said. “In meeting the primary endpoint of disease-free survival, C-POST has the potential to give clinicians another option for patients with difficult-to-treat squamous cancers of the skin who have a high risk of locoregional and/or systemic metastatic failure. That said, the lack of an overall survival advantage and the higher rate of high-grade toxicity in the cemiplimab-rwlc arm mean it is likely this treatment will be applicable only in selected groups of patients with limited comorbidities and a good performance status who have disease characteristics placing them in the highest risk groups for disease relapse.”
DISCLOSURE: Dr. Harrington has received institutional funding from Scientific Advisory Board/Steering Committee memberships with ALX Oncology, Amgen, Arch Oncology, AstraZeneca, BeiGene, Bicara Therapeutics, BMS, Boehringer Ingelheim, Eisai, GSK, Johnson & Johnson, Merck Serono, Merus, Molecular Partners, MSD, Nanobiotix, Onchilles Pharma, One-carbon Therapeutics, Outrun Therapeutics, PDS Biotech, Pfizer, PsiVac, QBiotics, Replimune, and VacV; and has received institutional research funding from AstraZeneca, Boehringer Ingelheimm and Replimune,
