Clinical and Patient-Reported Outcomes in C-POST: Phase 3 Trial of Adjuvant Cemiplimab Versus Placebo for High-Risk Cutaneous Squamous Cell Carcinoma

Background C-POST is a phase 3, double-blind, multicenter, placebo-controlled trial (NCT03969004) of adjuvant cemiplimab for the treatment of CSCC with high risk of recurrence after surgery and radiation therapy. We present the primary analysis including efficacy, safety, and PROs. Methods C-POST included patients with local and/or regional CSCC after surgery and post-operative radiation therapy, at high risk of recurrence based on nodal and/or non-nodal criteria. Patients were randomized 1:1 to cemiplimab 350 mg or placebo Q3W for 12 weeks, then cemiplimab 700 mg or placebo Q6W up to 36 weeks (up to 48 weeks total). Crossover was allowed after disease recurrence. The primary endpoint was disease-free survival (DFS). Secondary endpoints included freedom from local-regional recurrence (FFLRR), freedom from distant recurrence (FFDR), overall survival (OS), and safety. The pre-specified PRO analysis focused on QLQ-C30 global health status/quality of life (GHS/QoL), functional (physical, role, emotional), and symptom (fatigue, pain) scales. Overall PRO changes from baseline across treatment cycles were analyzed using mixed-effects models for repeated measures. The PRO responder analysis used a 10-point threshold for clinically meaningful change. The data cutoff (~50% of final DFS events; pre-specified threshold) was October 4, 2024. Results From June 2019 to August 2024, 415 patients (209/206 cemiplimab/placebo) were randomized: median age, 71 years (range 33–95); 83.9% male; 82.7% head and neck primary; 58.3%/41.7% high-risk nodal/non-nodal categories. Median (range) follow-up was 24 (2–64) months. DFS was superior with cemiplimab versus placebo (24 vs 65 events). Median DFS was not reached in the cemiplimab arm and was 49.4 months in the placebo arm; HR 0.32 (95% CI: 0.20–0.51; P<0.0001). Kaplan–Meier estimated 24-month DFS was 87.1% (95% CI: 80.3–91.6) for cemiplimab and 64.1% (95% CI: 55.9–71.1) for placebo. Cemiplimab improved FFLRR (HR 0.20; 95% CI: 0.09–0.40) and FFDR (HR 0.35; 95% CI: 0.17–0.72) versus placebo. Kaplan–Meier estimated 24-month FFLRR/FFDR was 94.6% (95% CI: 89.1–97.3)/94.3% (95% CI: 89.0–97.1) for cemiplimab and 76.7% (95% CI: 69.1–82.6)/83.8% (95% CI: 76.3–89.0) for placebo. OS HR (April 2025 data cutoff; 33 deaths) for cemiplimab versus placebo was 0.78 (95% CI: 0.39–1.56). Grade ≥3 treatment-emergent adverse events (TEAEs) occurred in 23.9% and 14.2%, and discontinuations due to TEAEs occurred in 9.8% and 1.5% of patients receiving cemiplimab and placebo, respectively. Overall changes from baseline on QLQ-C30 GHS/QoL, functioning, and symptom scores were small and similar between arms. Most patients in both arms reported maintenance or clinically meaningful improvement in QoL in all scales across all cycles (cemiplimab: 55.9–86.8%; placebo: 55.5–88.2%). Kaplan–Meier estimated median time to first deterioration in QoL was similar between arms in all scales (cemiplimab: 5.6–25.6 months; placebo: 8.3–22.2 months). Conclusion Cemiplimab is the first systemic adjuvant immunotherapy to demonstrate statistically significant and clinically meaningful reduction in disease recurrence for high-risk CSCC, and was consistent with the known safety profile of cemiplimab monotherapy in advanced or metastatic disease. QoL was maintained on cemiplimab, with no clinically meaningful differences versus placebo.