Clinical Summary

• Updated C-POST study results showed sustained disease-free survival benefit with adjuvant cemiplimab vs placebo after surgery and postoperative radiotherapy for high-risk cutaneous squamous cell carcinoma (HR, 0.46).
• At a median follow-up of 43.8 months, the overall survival hazard ratio decreased to 0.63 (95% CI, 0.36-1.11), although a statistically significant survival benefit has not been established.
• Exploratory circulating tumor DNA analysis showed disease-free survival benefit in both minimal residual disease-negative and -positive subgroups, supporting adjuvant cemiplimab regardless of baseline minimal residual disease status.

Danny Rischin, MD, MBBS, FRACP, a medical oncologist at Peter MacCallum Cancer Centre in Melbourne, Australia, discusses updated results from the phase 3 C-POST trial presented at the 2026 ESMO Congress. Adjuvant cemiplimab maintained a disease-free survival benefit following surgery and postoperative radiotherapy for high-risk cutaneous squamous cell carcinoma (HR, 0.46). At a median follow-up of 43.8 months, the overall survival hazard ratio was 0.63 (95% CI, 0.36-1.11), despite 88% of patients with recurrence in the placebo arm crossing over to cemiplimab; this finding remains statistically inconclusive.

An exploratory circulating tumor DNA analysis included 191 patients, approximately 18% of whom had detectable minimal residual disease before adjuvant treatment. Detectable disease was associated with poorer prognosis, particularly in the placebo arm, but cemiplimab favored disease-free survival in both minimal residual disease-negative and -positive subgroups. These findings reinforce adjuvant cemiplimab use rather than waiting for recurrence and suggest that undetectable minimal residual disease alone should not exclude otherwise eligible patients from treatment.

Transcript

My name is Danny Rischin. I'm a medical oncologist from the Peter MacCallum Cancer Centre in Melbourne, Australia. I was the principal investigator on the C-POST trial. The C-POST trial is a phase 3 trial that established adjuvant cemiplimab, an anti-PD-1 antibody, as a standard of care for patients with high-risk cutaneous squamous cell carcinoma (SCC). 

In this trial, patients with high-risk criteria, which could be nodal or nonnodal, after completion of surgery and postoperative radiotherapy were randomized to cemiplimab or placebo for 48 weeks. The study met its primary end point at the first analysis, with a hazard ratio for disease-free survival of 0.32. Overall survival data were immature, with a hazard ratio of 0.86 at that time. 

At ESMO this year, we have provided updated overall survival, disease-free survival results, and also the results of an exploratory analysis of circulating tumor DNA (ctDNA) detection of minimal residual disease (MRD).

First of all, in terms of overall survival, with a median follow-up of 43.8 months, the hazard ratio for overall survival has decreased to 0.63. The 95% confidence limits were 0.36 to 1.11. And this is despite the fact that of the patients on the placebo arm who recurred, 88% of them crossed over to receive cemiplimab. In terms of disease-free survival, we saw continued benefit with a hazard ratio of 0.46.

This ctDNA analysis was done using a tumor-informed, ultrasensitive next-generation sequencing assay. This was done as part of a protocol amendment during the study, and we ended up with samples from 191 patients. Of these patients, approximately 18% had ctDNA detectable. This was detectable after the completion of surgery and postoperative radiotherapy and before the commencement of any adjuvant treatment. 

We found that patients who were MRD positive, particularly in the placebo arm, had a poorer prognosis. But in terms of the benefit from cemiplimab vs placebo, we saw that regardless of MRD status. In patients who were MRD negative, there was a hazard ratio of 0.45 favoring cemiplimab. And in the patients who were MRD positive, the hazard ratio was 0.24, again favoring cemiplimab.

In conclusion, the results of this analysis, with the decreasing hazard ratio for overall survival and a continued disease-free survival benefit, support the use of adjuvant cemiplimab rather than waiting for recurrence. Furthermore, the MRD analysis suggests that patients benefited from cemiplimab regardless of their MRD status.

Source:

Gross N, Miller DM, Khushalani NI, et al. A phase 2 study of neoadjuvant cemiplimab for stage II–IV cutaneous squamous cell carcinoma (CSCC): Final analysis. Presented at ESMO Congress. October 23-27, 2026; Madrid, Spain. Abstract 2490P.