Adjuvant Cemiplimab Improves DFS in High-Risk Cutaneous Squamous Cell Carcinoma

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Cemiplimab-rwlc (Libtayo) led to a statistically significant and clinically meaningful improvement in disease-free survival (DFS) as adjuvant therapy vs placebo in patients with high-risk cutaneous squamous cell carcinoma (CSCC) after surgery, meeting the primary end point of the phase 3 C-POST trial (NCT03969004).¹

At the first prespecified interim analysis for DFS with a median follow-up of 24 months (range, 2-64), cemiplimab reduced the risk of disease recurrence or death by 68% vs placebo (HR, 0.32; 95% CI, 0.20-0.51; P < .0001).

Regarding safety, which was evaluated in 205 patients in the cemiplimab arm and 204 patients in the placebo arm, any-grade adverse effects (AEs) occurred in 91% and 89% of patients, respectively. Grade 3 or greater AEs occurred in 24% and 14% of patients, respectively. AEs leading to treatment discontinuations occurred in 10% and 1.5% of patients, respectively. Two patients experienced an AE leading to death in each arm.

The trial will continue for additional follow-up, including an analysis of the key secondary end point of overall survival (OS). Additional data will be presented at an upcoming medical meeting and shared with regulatory agencies along with a plan for FDA submission in the first half of 2025.

“While surgery is curative for most people living with CSCC, many are burdened with a higher risk of recurrence that can lead to death or disfiguration,” 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, stated in a news release. “At the first prespecified interim analysis, [cemiplimab] achieved a remarkably high bar in improving DFS in high-risk CSCC. 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.”

Within CSCC cemiplimab is only indicated for the treatment of patients with metastatic CSCC or locally advanced CSCC who are not candidates for curative surgery or curative radiation.²

C-POST is an ongoing randomized, placebo-controlled, double-blind, multicenter, global trial investigating adjuvant cemiplimab vs placebo in 415 patients with high-risk CSCC following surgery and postoperative radiation therapy.¹ High-risk features will be based on nodal features (extracapsular extension or ≥ 3 involved lymph nodes) and/or non-nodal features (in-transit metastases, T4 lesion, perineural invasion, or locally recurrent tumor with ≥ 1 additional poor prognostic features).

Eligible patients will receive either 350 mg of intravenous cemiplimab or placebo every 3 weeks for the first 12 weeks, followed by an escalated dose of 700 mg of cemiplimab or placebo based on randomization every 6 weeks for 36 weeks.

The primary end point is DFS; secondary end points include freedom from locoregional recurrence, freedom from distant recurrence, OS, cumulative incidence of second primary CSCC tumors, and safety.

“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 CSCC and has become a standard of care in this setting,” Israel Lowy, MD, PhD, Clinical Development Unit Head, Oncology, at Regeneron, stated in the news release. “With these results, [cemiplimab] now has the potential to also transform the treatment of high-risk resectable CSCC 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.”

References

1. 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. January 13, 2024. Accessed January 13, 2024. https://investor.regeneron.com/news-releases/news-release-details/adjuvant-libtayor-cemiplimab-significantly-improves-disease-free
2. FDA approves cemiplimab-rwlc for metastatic or locally advanced cutaneous squamous cell carcinoma. FDA. Updated January 18, 2019. Accessed January 13, 2025. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-cemiplimab-rwlc-metastatic-or-locally-advanced-cutaneous-squamous-cell-carcinoma#:~:text=On%20Sept.,curative%20surgery%20or%20curative%20radiation.