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Cemiplimab wins EU approval after C-POST shows DFS gains for high-risk CSCC, marking the first effective adjuvant immunotherapy option.
The European Commission has approved cemiplimab-rwlc (Libtayo) for adjuvant use in adult patients with cutaneous squamous cell carcinoma (CSCC) at high recurrence risk following surgery and radiation.1
The regulatory decision was based on findings from the phase 3 C-POST trial (NCT03969004) in which adjuvant cemiplimab (n = 209) led to a median disease-free survival (DFS) that was not reached (95% CI, not evaluable [NE]-NE) vs 49.4 months (95% CI, 48.5-NE) with placebo (n = 206; HR, 0.32; 95% CI, 0.20-0.51; P < .001).2 The percentages of patients who received the immunotherapy and were free from disease recurrence at 12, 24, and 26 months were 92.4%, 87.1%, and 83.1%, respectively; in those who received placebo, these respective rates were 69.5%, 64.1%, and 60.4%.
“While CSCC can often be treated successfully with surgery and radiation, some patients face the persistent threat of disease recurrence and potentially fatal outcomes. This highlights a critical need for earlier intervention, but immunotherapy has until now been reserved just for advanced cases,” Paolo Bossi, MD, head of the Head and Neck Medical Oncology Unit and associate professor of Medical Oncology at Humanitas University and Humanitas Cancer Center, in Milan, Italy, stated in a news release.1 “As the only immunotherapy shown to improve disease-free survival in this setting, Libtayo could change the outlook for these earlier-stage patients in need.”
The international phase 3 trial enrolled patients with local or regional CSCC who had completed curative-intent surgery, had macroscopic gross resection of all disease, and received post-operative radiation or concurrent chemoradiation at a dose of at least 50 Gy within 2 to 10 weeks prior to randomization.2 Patients were at least 18 years of age and had high-risk nodal, nonmodal features, or both. If they had concurrent cancer, had undergone prior solid organ or stem cell transplant, had clinically significant autoimmune disease, or had prior exposure to immunotherapy for CSCC, they were excluded.
For part 1 of the research, participants were randomly assigned 1:1 to receive the immunotherapy or placebo. Under a protocol amendment made on June 29, 2021, cemiplimab was administered at 350 mg every 3 weeks (Q3W) for 12 weeks; the immunotherapy was then given at 700 mg every 6 weeks (Q6W) for an additional 36 weeks. Placebo was given Q3W for 12 weeks; it was then given Q6W for an additional 36 weeks. Treatment would continue until recurrence, intolerable toxicity, withdrawn consent, or for up to 48 weeks.
Stratification factors included tumor location (head and neck vs non–head and neck), geographic region (North America vs Australia vs New Zealand vs rest of world), high-risk category (nodal vs nonmodal), ECOG performance status (0 vs 1), and chronic lymphocytic leukemia history (yes vs no).
For part 2, those who received placebo and experienced recurrence or those who received the immunotherapy and experienced recurrence that happened at least 3 months following part 1 completion, are able to receive subsequent cemiplimab.
The primary end point of the trial was DFS, and secondary end points comprised freedom from locoregional recurrence and distant recurrence, overall survival (OS), second primary CSCC tumors, and safety. Investigators will also examine patient-reported outcomes as an exploratory end point.
The median patient age across the cemiplimab and placebo arms was 70.5 years (range, 33-95) and more than half were at least 65 years (73.2% vs 68.4%). Most patients were White (90.4% vs 91.7%), had an ECOG performance status of 0 (63.6% vs 63.6%), had their high-risk tumor located in the head and neck area (79.4% vs 85.9%), fell into a high-risk category of nodal (59.8% vs 56.8%), and a PD-L1 tumor proportion score of 1% or higher (74.2% vs 74.8%). Just under half of patients were from Australia or New Zealand (43.1% vs 43.7%).
Additional data published in the New England Journal of Medicine showed that the immunotherapy prolonged freedom from locoregional (HR, 0.20; 95% CI, 0.08-0.40) and distant recurrences (HR, 0.35; 95 % CI, 0.17-0.72) vs placebo.
At the time of the data cutoff date, 25 deaths had been recorded. The 2-year OS rate with cemiplimab was 94.8% (95% CI, 89.6%-97.4%) vs 92.3% (95% CI, 86.5%-95.7%) with placebo (HR, 0.86; 95% CI, 0.39-1.90). At a later data cutoff date of April 7, 2025, 33 deaths had been reported, and the HR for OS was 0.78 (95% CI, 0.39-1.56).
Any-grade adverse effects (AEs) occurred in 91.2% of patients and they were grade 3 or higher for 23.9% of patients. Serious toxicities were observed in 17.6% of patients who received the immunotherapy, with 15.1% of cases being grade 3 or higher in severity. AEs led to discontinuation for 9.8% of those who received cemiplimab; 2 AEs proved fatal.
The most common AEs experienced by at least 10% of patients in the cemiplimab arm included fatigue (any grade, 22.0%; grade ≥3, 0.5%), pruritus (16.1% vs 0.5%), rash (16.1% vs 0.5%), diarrhea (15.6% vs 1.5%), arthralgia (12.7%; 0%), hypothyroidism (11.7% vs 0.5%), maculopapular rash (11.2%; 0%), and Bowen’s disease (7.8%; 0.5%).
In October 2025, the FDA approved cemiplimab for adjuvant use in adult patients with CSCC at high risk of recurrence after surgery and radiation based on data from C-POST.3 In an exclusive interview4 with OncLive®, which also aired as an OncLive On Air podcast episode,5Vishal A. Patel, MD, FAAD, FACMS, explained the clinical significance of the decision: “The approval of cemiplimab for adults with CSCC at high risk of recurrence after surgery and radiation represents a major advance for our patients and for the field,” he said.6 “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.”
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