By Ying Hitchcock, MD, FASTRO, Huntsman Cancer Hospital, University of Utah
Danny Rischin, MD, is a medical oncologist/clinician researcher at the Peter MacCallum Cancer Centre in Melbourne, Australia. He has played a leading role in the pivotal trials defining the role of immunotherapy in cutaneous SCC, in both the advanced (unsuitable for surgery and/or metastatic) setting as well as in the locoregionally advanced group suitable for curative surgery/PORT.
The C‑POST trial represents a pivotal advance in the management of high‑risk cutaneous squamous cell carcinoma (CSCC), a disease for which no adjuvant systemic therapy has previously demonstrated clinical benefit. Patients with high‑risk CSCC — particularly those with nodal involvement, extensive perineural invasion or deeply infiltrative tumor, experience recurrence rates comparable to other aggressive epithelial cancers. The introduction of adjuvant immunotherapy has therefore been long anticipated, and the results presented by Dr. Dan Rischin and colleagues provide the first definitive evidence supporting this strategy.
Between June 2019 and August 2024, 415 patients were randomized 1:1 to receive cemiplimab or placebo following surgery and postoperative radiation. Treatment consisted of cemiplimab 350 mg or placebo every three weeks for 12 weeks, followed by cemiplimab 700 mg or placebo every six weeks for up to 36 additional weeks. The primary endpoint, disease‑free survival (DFS), demonstrated a striking benefit: the hazard ratio of 0.32 corresponds to reduction in recurrence or death, a magnitude rarely observed in adjuvant oncology. Median DFS was not reached in the cemiplimab arm, compared with 49.4 months for placebo, and the 24‑month DFS rates (87% vs. 64%) highlight the durability of benefit.
The advantage extended across recurrence patterns. Freedom from local‑regional recurrence (HR 0.20) and freedom from distant recurrence (HR 0.35) both favored cemiplimab, strongly suggesting that PD‑1 blockade effectively eradicates micrometastatic disease in this population. Although overall survival data remain immature, the DFS signal is sufficiently compelling to support clinical adoption. The trial’s crossover design, while ethically appropriate, may attenuate future OS differences, a common challenge in contemporary immunotherapy trials.
Cemiplimab’s safety profile was consistent with prior experience. Grade ≥3 treatment‑emergent adverse events occurred in 24% of patients receiving cemiplimab versus 14% with placebo, and discontinuation rates (10% vs. 2%) were acceptable in a curative‑intent setting. No unexpected toxicities emerged, an important consideration given the older median age of the cohort (71 years).
A notable strength of C‑POST is its incorporation of patient‑reported outcomes (PROs), essential for evaluating adjuvant therapy in an elderly population. Across global quality of life, functional domains and symptom scales, changes from baseline were small and comparable between arms. Most patients reported stable or improved quality of life, and time to the deterioration did not differ meaningfully. These findings reinforce that the substantial DFS benefit of cemiplimab is not offset by a decline in patient well‑being.
Overall, C‑POST establishes adjuvant cemiplimab as the first effective systemic therapy for high‑risk CSCC. Its compelling efficacy, manageable safety profile and preserved quality of life support its integration into standard practice and mark a transformative step forward in CSCC management.
Published February 20, 2026
