Defining High-Risk CSCC: C-POST Patient Criteria Explained

In an interview with Targeted Oncology, Vishal A. Patel, MD, associate professor of Dermatology and of Medicine (Hematology/Oncology) at George Washington (GW) University School of Medicine and Health Sciences and director, Cutaneous Oncology Program at GW Cancer Center, provides a high-level overview of the pivotal phase 3 C-POST trial (NCT03969004)—the underpinnings of the FDA’s recent approval of adjuvant cemiplimab (Libtayo) in high-risk cutaneous squamous cell carcinoma (CSCC) on October 8, 2025—and dives deep into the high-risk criteria used to capture the patient population most in need.

Read the full interview here.

The C-POST trial is a randomized, double blind, placebo-controlled phase 3 trial evaluating adjuvant cemiplimab in adult patients with CSCC who underwent surgical resection and radiation therapy and subsequently remained at high risk for recurrence. The primary end point of the study was disease-free survival; key secondary end points included freedom from locoregionally recurrence, freedom from distant recurrence, and safety.

Dr Patel elaborates on the definition of “high risk” used to capture the patient population and tumors with the highest risk of recurrence, which were informed by previous CSCC studies. The criteria included patients with specific nodal disease, including a lymph node larger than 2 cm with extracapsular extension, or multiple lymph nodes regardless of size. It also included tumors with non-nodal high-risk features, including those that had in-transit metastases, invaded the bones, tumors with perineural invasion that caused symptoms identifiable on radiographic imaging, as well as locally recurrent tumors with an additional risk factor such as poor differentiation or size.

“Understanding [the study population] is key to understanding the significance of this trial. Eligibility deliberately targeted patients we worry about the most,” Patel explained during the interview.

In total, the study enrolled 415 patients who collectively completed curative intent surgery and postoperative radiation therapy before being randomized to receive either cemiplimab or placebo, which helped focus the research on examining the added value of cemiplimab to local therapy. The treatment regimen, with a total duration of 48 weeks, consisted of the standard 358-mg dosing of cemiplimab every 3 weeks for the first 12 weeks, followed by switching to a higher 700-mg dose every 6 weeks for up to 36 more weeks.