Cemiplimab Improves Disease-Free Survival in High-Risk, Advanced CSCC

Cemiplimab (Libtayo; Regeneron) showed efficacy in high-risk patients with cutaneous squamous cell carcinoma (CSCC) and in the real-world setting in abstracts from the 2025 American Society of Clinical Oncology (ASCO) annual meeting.^1,2

Cemiplimab is a monoclonal antibody targeting PD-1, and it was approved by the FDA in 2018 for the treatment of metastatic or locally advanced CSCC.³ In clinical trials, 47% of patients had a response to therapy, and a majority of responders had a duration of response exceeding 6 months.⁴

Patients in the cemiplimab group had superior disease-free survival vs placebo. | Image credit: Medical Works - stock.adobe.com

One of the abstracts presented at ASCO was an analysis of the phase 3 C-POST trial (NCT03969004) of cemiplimab vs placebo in patients with local and/or regional CSCC who were at a high risk of recurrence following surgery and postoperative radiation.¹ The research was important because there is currently no approved therapy for this specific patient group, the authors explained.

In the trial, 415 patients were recruited who had undergone definitive local therapy but met criteria for being at a high risk of recurrence either due to nodal or non-nodal features. Those patients were randomized 1:1 to receive either cemiplimab or placebo. Those in the cemiplimab group received a dose of 350 mg every 3 weeks for 12 weeks, followed by 700 mg doses every 6 weeks for up to 36 weeks. Patients in the placebo group were allowed to cross over into the therapy group after disease recurrence.

Patients were enrolled between June 2019 and August 2024. Most (84%) were male, most (83%) had primary head and neck cancers, and the group had a median age of 71 years.

At a median follow-up of 24 months, patients in the cemiplimab group had superior disease-free survival (HR, 0.32; 95% CI, 0.20-0.51; P < .0001). The estimated 24-month disease-free survival was 87% (95% CI, 80-92) for patients receiving cemiplimab compared with 64% (95% CI, 56-71) for patients in the placebo cohort.

The trial’s secondary end points included freedom from local-regional recurrence, freedom from distant recurrence, and overall survival. Cemiplimab had superior outcomes on all 3 secondary end points.

In terms of safety about one-quarter of patients (23.9%) taking cemiplimab experienced grade 3 or above treatment-emergent adverse events, and 9.8% of patients discontinued the therapy as a result of adverse events. In the placebo group, the rates of adverse events and discontinuation were 14.2% and 1.5%, respectively.

“Cemiplimab is the first systemic therapy to demonstrate a statistically significant and clinically meaningful reduction in disease recurrence as adjuvant therapy for high-risk CSCC, and has an acceptable safety profile in this setting,” the authors concluded.

Another abstract outlined interim results from a real-world study looking at the therapy’s safety and efficacy in an advanced CSCC population.² The trial’s investigators recruited 254 patients with locally advanced (64.2%) or metastatic (35.8%) CSCC. Seventeen percent of participants were immunocompromised or immunosuppressed. All of the participants had at least 1 dose of cemiplimab, and the median duration of exposure was 35 weeks. Most of the participants (78.3%) were male, and most (82.7%) were 65 years old or older. 

The overall response rate was 43.7% (95% CI, 37.5-50.0), and the complete response rate was 15.7% in the overall study population. When the investigators excluded patients with missing response data, the overall response rate and complete response rate for patients with at least 1 response assessment were 55.2% (95% CI, 48.1-62.2) and 19.9%, respectively. The study’s median progression-free survival was 14.7% (95% CI, 12.5-21.1) and the 12-month survival rate was 59.5% (95% CI, 51.4-66.7).

“The interim results of this phase 3 study demonstrate robust effectiveness and a generally manageable safety profile of cemiplimab in patients with laCSCC/mCSCC in real-world practice that are comparable to the results of the EMPOWER-CSCC-1 trial,” the authors concluded.

References

1. 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: ASCO 2025; May 30-June 3, 2025; Chicago, Illinois. Abstract 6001.

2. Park SJ, Rabinowitz G, Panella TJ, et al. Cemiplimab-rwlc survivorship and epidemiology (CASE): Interim results from a prospective study of the safety and effectiveness of cemiplimab in patients with advanced cutaneous squamous cell carcinoma (CSCC) in a real-world setting. Presented at: ASCO 2025; May 30-June 3, 2025; Chicago, Illinois. Abstract 9533.

3. FDA approves cemiplimab-rwlc for metastatic or locally advanced cutaneous squamous cell carcinoma. News release. FDA. Published September 28, 2018. Accessed June 9, 2025. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-cemiplimab-rwlc-metastatic-or-locally-advanced-cutaneous-squamous-cell-carcinoma 

4. Migden MR, Rischin D, Schmults CD, et al. PD-1 blockade with cemiplimab in advanced cutaneous squamous-cell carcinoma. N Engl J Med. 2018;379(4):341-351. doi:10.1056/NEJMoa1805131