Cemiplimab (PD-1) Cuts Recurrence Risk in High-Risk Resected CSCC—Consistent Across Risk Features and RT Timing

Cemiplimab (Libtayo) is an anti–PD-1 antibody tested as adjuvant systemic therapy after surgery plus postoperative radiotherapy in the Phase 3, double-blind C-POST trial (NCT03969004). In this exploratory DFS update at median 30 months’ follow-up (N=415; 209 cemiplimab/206 placebo; data cutoff April 7, 2025), cemiplimab improved DFS vs placebo (HR 0.35, 95% CI 0.23-0.55), with benefit seen across nodal and non-nodal “high-risk” definitions including ECE with ≥1 node ≥20mm (HR 0.44), ≥3 nodes (HR 0.34), in-transit metastases (HR 0.07), perineural invasion (HR 0.27, CI crosses 1), and recurrent CSCC with ≥1 additional risk feature (HR 0.19); the T4 subgroup was inconclusive (HR 0.58, wide CI 0.16-2.11). The DFS benefit was similar whether randomization occurred 2-6 weeks post-RT (DFS events 14.5% vs 33.0%; HR 0.39) or >6 weeks post-RT (13.2% vs 33.3%; HR 0.36); safety details weren’t expanded here, but prior primary reporting noted discontinuation due to AEs of 9.8% with cemiplimab vs 1.5% with placebo—against the historical post-op RT “SOC” of observation/no systemic therapy, this is essentially a new adjuvant benchmark rather than an incremental tweak.