FDA Approval of Cemiplimab: A New Era for High-Risk CSCC Treatment

In a significant step forward for skin cancer management, the U.S. Food and Drug Administration (FDA) has approved cemiplimab-rwlc (Libtayo) as an adjuvant treatment for adults with cutaneous squamous cell carcinoma (CSCC) at high risk of recurrence following surgery and radiation. The decision, announced on October 8, 2025, marks the first approval of a PD-1 inhibitor for this specific post-treatment setting in CSCC—a common yet potentially aggressive form of skin cancer.

The approval is backed by data from the C-POST trial (NCT03969004), a randomized, double-blind, placebo-controlled study involving 415 patients with CSCC who had completed curative-intent surgery and adjuvant radiation therapy. Patients enrolled in the trial had to initiate study treatment within two to ten weeks after completing radiation and were considered high-risk based on features such as tumor size, depth of invasion, perineural involvement, or nodal disease.

Participants were randomized to receive either cemiplimab or placebo, with the primary endpoint of disease-free survival (DFS) defined as time to recurrence or death. The trial yielded a compelling result: median DFS was not reached in the cemiplimab arm, compared with 49.4 months in the placebo group. The hazard ratio was 0.32 (95% CI: 0.20–0.51), indicating a 68% reduction in the risk of recurrence or death with cemiplimab. The statistical significance was robust, with a p-value less than 0.0001.

These findings underscore the growing recognition of immunotherapy’s role beyond metastatic disease, extending its utility into earlier stages of cancer treatment. For a disease like CSCC—where the majority of cases are cured with local therapy but a subset recurs with life-threatening consequences—this approval fills a long-standing gap in care for patients deemed high risk even after initial treatment success.

Cemiplimab, a fully human monoclonal antibody targeting PD-1, was already approved for advanced CSCC, among other indications. With this expanded use, clinicians now have an evidence-based option to reduce the risk of relapse in a particularly vulnerable group of patients. The treatment is administered at a dose of 350 mg intravenously every three weeks for 12 weeks, followed by 700 mg every six weeks, or continued at 350 mg every three weeks based on tolerability and risk profile, for up to 48 weeks or until disease recurrence or unacceptable toxicity.

The safety profile of cemiplimab remains consistent with other PD-1 inhibitors. The prescribing information includes boxed warnings for immune-mediated adverse events—such as pneumonitis, colitis, hepatitis, endocrinopathies, and nephritis—as well as infusion-related reactions and embryo-fetal toxicity. Importantly, patients with autoimmune disease requiring immunosuppression, prior organ transplantation, or uncontrolled viral infections were excluded from the C-POST trial, limiting generalizability to those populations.

The FDA’s review of this application utilized the Real-Time Oncology Review (RTOR) program, designed to accelerate review timelines by allowing early submission of pivotal data. It also incorporated the Assessment Aid, a structured summary submitted voluntarily by the sponsor, Regeneron Pharmaceuticals. The application was granted priority review, reflecting the agency’s recognition of cemiplimab’s potential to address a serious unmet need.

Healthcare professionals are urged to report any serious adverse events related to cemiplimab through the FDA’s MedWatch system, helping to monitor real-world safety as this therapy moves into broader clinical use.

For many oncologists and dermatologic surgeons, this approval represents a welcome addition to the post-operative arsenal in CSCC, particularly for patients with high-risk pathological features and limited options beyond surveillance. As immunotherapy continues to migrate earlier into cancer treatment paradigms, cemiplimab’s adjuvant role in CSCC may signal a broader shift toward preemptive strategies designed to preserve long-term remission—and perhaps, cure.