Adjuvant Cemiplimab Improves DFS in High-Risk CSCC
The C-POST trial has shown cemiplimab to significantly improve disease-free survival in patients with high-risk cutaneous squamous cell carcinoma following surgery.
Cutaneous squamous cell carcinoma - Generated with Google Gemini AI
Adjuvant treatment with cemiplimab (Libtayo) elicited a statistically significant and clinically meaningful improvement in the primary end point of disease-free survival (DFS) among patients with high-risk cutaneous squamous cell carcinoma (CSCC) after surgery, according to findings from the phase 3 C-POST trial (NCT03969004).1
With a 68% reduction in the risk of disease recurrence or death in patients with high-risk CSCC after surgery (HR, 0.32; 95% CI, 0.20-0.51; P <.0001) vs placebo at the first prespecified interim analysis for DFS with a median duration of follow-up of 24 months (range, 2-64 months), the primary end point of DFS has been met.
For safety, adverse events (AEs) of any grade occurred in 91% of patients in the cemiplimab arm (n = 205) and 89% of patients in the placebo arm (n = 204), respectively. Grade 3 or higher AEs were seen in 24% and 14% of patients in each arm, respectively, and 10% and 1.5% discontinued treatment due to AEs in the cemiplimab arm and the placebo arm, respectively. Moreover, AEs led to death in 2 patients per arm.
“While surgery is curative for most people living with cutaneous squamous cell carcinoma, many are burdened with a higher risk of recurrence that can lead to death or disfiguration,” said Danny Rischin, MD, MBBS, FRACP, research lead, head and neck cancer and cutaneous SCC, Department of Medical Oncology at the Peter MacCallum Cancer Centre in Melbourne, Australia, and lead investigator of the trial, in a press release. “At the first prespecified interim analysis, [cemiplimab] achieved a remarkably high bar in improving disease-free survival in high-risk cutaneous squamous cell carcinoma. With no currently approved options in the adjuvant setting, these landmark results demonstrate [cemiplimab] could represent a major advance in delaying recurrence in these vulnerable patients.”
Following these interim findings, the C-POST trial will continue to collect follow-up data, with a primary focus on assessing the critical secondary end point of overall survival (OS). Additional data are expected to be presented at an upcoming medical meeting and subsequently submitted to regulatory agencies.
Further, Regeneron anticipates filing a new drug application with the FDA in the first half of 2025.
“Regeneron has long been a pioneer in non-melanoma skin cancer research. [cemiplimab] was the first PD-1 inhibitor approved for certain patients with advanced cutaneous squamous cell carcinoma and has become a standard of care in this setting,” said Israel Lowy, MD, PhD, clinical development unit head, oncology, at Regeneron, in the press release. “With these results, [cemiplimab] now has the potential to also transform the treatment of high-risk resectable cutaneous squamous cell carcinoma with adjuvant treatment. This trial is a testament to our unrelenting commitment to investigating areas where patient need remains high and to pursuing clinical research across diverse stages of skin cancer.”
About the Phase 3 C-POST Trial
C-POST is an ongoing, pivotal phase 3 trial evaluating the efficacy and safety of cemiplimab vs placebo as adjuvant therapy for patients with CSCC at high risk of recurrence. High-risk features include nodal involvement and/or non-nodal factors.
The trial is utilizing a randomized, double-blind, placebo-controlled design across multiple international sites. Once enrolled, patients will receive either cemiplimab at a dose of 350 mg or placebo intravenously every 3 weeks for 12 weeks, followed by cemiplimab 700 mg or placebo every 6 weeks for an additional 36 weeks.2
This study includes patients aged 18 years and older who have undergone resection of pathologically confirmed CSCC, including primary CSCC alone, primary CSCC with nodal involvement, or nodal metastases from a known primary CSCC lesion previously treated within the respective draining lymph node basin. Macroscopic gross resection of all visible disease is required. Patients must be classified as having high-risk CSCC according to the study protocol. Completion of curative-intent postoperative radiation therapy within 2 to 10 weeks of randomization is mandatory and patients must have an ECOG performance status of ≤1. Further, patients must have adequate hepatic, renal, and bone marrow function as defined within the study protocol.
The primary end point is DFS, and key secondary end points include locoregional recurrence-free survival, distant recurrence-free survival, OS, the cumulative incidence of second primary CSCC tumors, and the assessment of treatment-related AEs.
The Trans-Tasman Radiation Oncology Group collaborated with Regeneron in the development of the C-POST trial protocol.1 The study includes 24 participating sites within Australia.
REFERENCES:
Adjuvant libtayo® (cemiplimab) significantly improves disease-free survival (DFS) after surgery in high-risk cutaneous squamous cell carcinoma (CSCC) in phase 3 trial. News release. Regeneron Pharmaceuticals, Inc. January 13, 2025. Accessed January 13, 2025. https://tinyurl.com/46b9f65k
Study of adjuvant cemiplimab versus placebo after surgery and radiation therapy in patients with high risk cutaneous squamous cell carcinoma. ClinicalTrials.gov. Updated September 19, 2024. Accessed January 13, 2025. https://clinicaltrials.gov/study/NCT03969004
