Adjuvant Immunotherapy Reduces Recurrence Risk in High-Risk Cutaneous Squamous Cell Carcinoma

Original Article : Adjuvant Cemiplimab or Placebo in High-Risk Cutaneous Squamous-Cell Carcinoma (C-POST Trial)

What are the key takeaways of this article?

Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer. Surgery remains a cornerstone treatment for many  patients, but those with high-risk features such as large or multiple involved lymph nodes, perineural invasion, bone invasion, or locally recurrent tumor face a recurrence rate around 45% even after surgery plus postoperative radiotherapy. Until recently, no adjuvant systemic therapy had been shown to change this. A prior phase 3 trial of adjuvant pembrolizumab (KEYNOTE-630) was stopped early for futility. Cemiplimab is an anti-PD-1 antibody already approved for advanced and metastatic cSCC since 2018, but it had never been tested in the post-curative-intent setting until this C-POST randomized trial.

This was a randomized, double-blind, placebo-controlled phase 3 trial that enrolled 415 adults across 16 countries between 2019 and 2024. All patients had completed surgery and postoperative radiotherapy for high-risk cSCC. They were randomized 1:1 to cemiplimab or placebo for a total of up to 48 weeks. Cemiplimab was dosed at 350 mg intravenously every three weeks for the first 12 weeks, then increased to 700 mg every six weeks for up to 36 more weeks. Most patients were elderly, male, white, and had head and neck primaries, which is typical for this disease. The primary endpoint was investigator-assessed disease-free survival (DFS).

At a median follow-up of 24 months, the results were compelling. Only 24 patients on cemiplimab had a DFS event versus 65 on placebo, a 68% reduction in the risk of recurrence or death (HR 0.32; P<0.0001). The 24-month disease-free survival rates were 87% versus 64%. Cemiplimab reduced both locoregional recurrence (HR 0.20) and distant recurrence (HR 0.35), and the benefit held across subgroups including patients with low PD-L1 expression. Overall survival data is immature (HR 0.78), so whether disease-free survival translates into longer life is still uncertain. Grade 3 or higher adverse events occurred in 24% of cemiplimab patients versus 14% on placebo, and roughly 10% discontinued treatment due to adverse events.

These findings have influenced clinical practice and led to FDA approval of adjuvant cemiplimab for high-risk cSCC in October 2025, making it the first systemic adjuvant therapy ever approved for this disease. The disease-free survival benefit is striking, but the lack of a proven overall survival benefit and the higher toxicity rate mean decisions still need to be made on an individual basis. Longer follow-up is needed to clarify whether reducing recurrence ultimately translates to improved survival.

Publication Date: June 15, 2026

Reference:

Rischin D, Porceddu S, Day F, et al; C-POST Trial Investigators. Adjuvant cemiplimab or placebo in high-risk cutaneous squamous-cell carcinoma. N Engl J Med. 2025;393(8):774-785. https://doi.org/10.1056/NEJMoa2502449

Summary By: Adam Ali Hussain