Libtayo Shows Promise as Adjuvant Therapy in High-Risk CSCC: Phase 3 C-POST Trial Results Advances

Recently published results from a phase 3, randomized trial in The New England Journal of Medicine reported compelling evidence supporting the use of systemic adjuvant Libtayo (cemiplimab) for patients with high-risk cutaneous squamous-cell carcinoma (CSCC) following surgery and radiation. The C-POST trial evaluated 415 patients with local or regional CSCC who had undergone definitive local therapy but faced high recurrence risk due to nodal or nonnodal features. Patients were randomized to receive either Libtayo or placebo, administered intravenously, over the course of up to 48 weeks. Disease-free survival (DFS) was the primary endpoint, with secondary endpoints including freedom from locoregional recurrence, freedom from distant recurrence, and safety. 

Results demonstrated a significant improvement in DFS among those treated with Libtayo. At 24 months, the estimated DFS was 87.1% with Libtayo vs 64.1% with placebo. The benefit extended to both locoregional and distant recurrence. The estimated percentage of patients free from locoregional recurrence in the Libtayo group was 94.6% at 24 months and 76.7% in the placebo group. The estimated percentage of patients free from distant recurrence in the Libtayo group was 94.3% at 24 months and 83.8% in the placebo group. This represents an 80% and a 65% reduction in the risk of locoregional and distant recurrence, respectively.  

Notably, subgroup analysis indicated the DFS benefit was maintained across diverse patient subsets, regardless of age, tumor location, or PD-L1 expression. While overall survival data are still maturing, early trends are encouraging. Additionally, patients who recurred after placebo were often re-treated with Libtayo, with many achieving positive outcomes. 

The safety profile of Libtayo was consistent with prior experience in advanced CSCC. While Grade ≥3 adverse events occurred more frequently with Libtayo (23.9% vs 14.2%), most were manageable, and overall quality of life was preserved during treatment. The most common adverse events with Libtayo compared with placebo were fatigue, pruritus, rash, and diarrhea. Immune-related adverse events were more common with Libtayo (22.9% vs 6.4%), though serious events were infrequent. 

In conclusion, adjuvant Libtayo represents a meaningful advance in the management of high-risk CSCC, offering prolonged disease control and a consistent safety profile in the context of advanced or metastatic disease. These findings may help reshape practice guidelines and provide new hope for patients at risk for recurrence. 

Reference:  

Rischin D, Porceddu S, Day F, et al. Adjuvant cemiplimab or placebo in high-risk cutaneous squamous-cell carcinoma. N Engl J Med. Published online May 31, 2025. doi:10.1056/NEJMoa2502449