Dr Patel on the FDA Approval of Adjuvant Cemiplimab for High-Risk Cutaneous Squamous Cell Carcinoma

“The approval of cemiplimab for adults with cutaneous squamous cell carcinoma at high risk of recurrence after surgery and radiation represents a major advance for our patients and for the field. Until now, these patients often with large nodal disease, extracapsular extension, perineural invasion that's clinically or radiographically significant, or deeply invasive tumors that go down to the bone, had no real proven systemic adjuvant option. And even after surgery and radiation, the recurrence risk remained substantial, [which] created a real unmet need.”

Vishal A. Patel, MD, associate professor of dermatology at the George Washington University School of Medicine & Health Sciences and director of the Cutaneous Oncology Program at the George Washington Cancer Center, discussed the clinical relevance of the FDA approval of cemiplimab-rwlc (Libtayo) for the adjuvant treatment of adult patients with cutaneous squamous cell carcinoma (CSCC) at high risk of recurrence following surgery and radiation therapy. The regulatory decision was supported by findings from the phase 3 C-POST trial (NCT03969004), which evaluated the efficacy and safety of adjuvant cemiplimab versus placebo in this high-risk population.

Patel noted that patients with CSCC at high risk of recurrence—such as those with large nodal invasion, perineural spread, or deep tumors often experience poor long-term outcomes despite optimal surgical resection and postoperative radiotherapy. Before this approval, immunotherapy was reserved for advanced or unresectable disease, leaving patients with resected high-risk CSCC without an evidence-based systemic option to reduce recurrence risk.

Findings from the C-POST trial that supported the approval demonstrated a statistically significant improvement in disease-free survival (DFS) with adjuvant cemiplimab compared with placebo. The median DFS was not reached (95% CI, not evaluable [NE]-NE) for patients treated with cemiplimab vs 49.4 months (95% CI, 48.5-NE) for those given placebo, corresponding to a 68% reduction in the risk of recurrence or death (HR, 0.32; 95% CI, 0.20-0.51; P < .0001). These results establish cemiplimab as the first immune checkpoint inhibitor to show a recurrence-prevention benefit in the adjuvant CSCC setting, Patel said.

He explained that this approval represents a shift toward earlier integration of PD-1 blockade in the treatment paradigm for CSCC, expanding its use beyond the advanced setting to improve long-term disease control following curative-intent therapy. The safety profile of cemiplimab was consistent with that observed in prior studies, with immune-related adverse effects largely manageable through standard treatment algorithms.

Patel concluded that adjuvant cemiplimab provides clinicians with a new therapeutic tool to address the unmet need for recurrence prevention in patients with resected, high-risk CSCC. The approval supports a more proactive approach to immunotherapy, aiming to reduce relapse rates and improve survival outcomes in this high-risk population.