Danny Rischin, MD, Peter MacCallum Cancer Centre, Melbourne, Australia, discusses the results from the phase 3 C-POST trial investigating adjuvant cemiplimab for patients with high-risk cutaneous squamous cell carcinoma (SCC). In this setting, cemiplimab showed a clinically meaningful and statistically significant improvement of disease-free survival. That improvement was seen across all pre-specified subgroups and included a decrease of both locoregional recurrence and distant metastases.

Dr Rischin concluded, “cemiplimab as adjuvant therapy for patients at high-risk of recurrence of cutaneous SCC can now be considered a potential new standard-of-care option.”

These data were first presented at the 2025 American Society for Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois.

Transcript:

My name's Danny Risin. I'm a medical oncologist from the Peter MacCallum Cancer Center in Melbourne, Australia, and I was the lead investigator on the C-POST trial, which was presented at ASCO this year.

The C-POST trial was an adjuvant trial of the anti–PD-1 targeting therapy cemiplimab compared to placebo in patients at high risk for recurrence of cutaneous SCC [squamous cell carcinoma]. The background to the trial is that although the great majority of patients with cutaneous SCC are cured with surgery alone, there remains a subset of patients who are at high risk of relapse despite having surgery and radiotherapy. We know that cemiplimab is standard of care in patients with more advanced disease, metastatic or locally advanced disease, not suitable for surgery or radiotherapy in that setting, and has a response rate of 47% of durable responses. But in this trial, we set out to find if using cemiplimab in an earlier stage of disease, locally advanced disease, could improve the outcomes for these patients and decrease the risk of recurrence.

The design of the trial was patients had surgery, if they were identified to have high-risk features, they went on to receive postoperative radiation and then they were randomized 1-to-1 to cemiplimab or placebo for 12 months. Important aspect of this trial was the high-risk criteria that we used to identify patients. We were aiming for a group of patients that had about a 45% risk of relapse. This included patients with high-risk nodal features, such as extra capsule extension, as long as there was a node, there was at least 20 mm or 3 or more nodes. Or some of the non-nodal features, such as intransient metastasis, T4 disease, a fairly advanced perineural invasion, and some patients had recurrent disease with adverse features.

The key results from the trial for the primary end point of disease-free survival was that the addition of cemiplimab as adjuvant therapy markedly improved disease-free survival compared to placebo. The hazard ratio was 0.32, P-value was less than 0.0001. We saw a marked early separation of the curves and that separation was maintained throughout the duration of follow up. The early drop off in disease-free survival that we saw in the placebo arm is atypical of what we expect with patients with cutaneous squamous cell carcinoma. The median disease-free survival was not reached in the cemiplimab arm. It was 49 months in the placebo arm. At 2 years, the disease-free survival was 87% in the cemiplimab arm and 64% in the control arm. 

This improvement in disease-free survival was due to both a significant decrease in locoregional recurrences and in distant metastasis. There was an 80% reduction in locoregional recurrences and a 65% reduction in distant metastasis. This benefit seen in disease-free survival was seen across all pre-specified subgroups. It was seen both in the patients with nodal high-risk criteria, the non-nodal high-risk criteria, and irrespective of PD-L1 expression. The drug was well tolerated. The safety profile was very much typical for an anti–PD-1 and consistent with the known profile of cemiplimab monotherapy.

In conclusion, cemiplimab is the first therapy in an adjuvant setting for high-risk cutaneous SCC to show in a clinically meaningful and statistically significant way that disease-free survival can be improved. With the hazard ratio of 0.32, this benefit was seen in all pre-specified subgroups and it was manifested both as a decrease in locoregional recurrences and a decrease in distant metastases. It had acceptable safety profile. Cemiplimab as adjuvant therapy for patients at high-risk of recurrence of cutaneous SCC can now be considered a potential new standard-of-care option.

Source:

Rischin D, Porceddu SV, Day F, et al. Phase 3 trial of adjuvant cemiplimab (cemi) versus placebo (pbo) for high-risk cutaneous squamous cell carcinoma (CSCC). Presented at the 2025 ASCO Annual Meeting. May 30-June 3, 2025; Chicago, IL. Abstract: 6001