Pembrolizumab (PD-1) + definitive CRT improves 5-year EFS in PD-L1 CPS≥10 unresected LA HNSCC

Pembrolizumab is a PD-1 checkpoint inhibitor added concurrently to definitive cisplatin-based chemoradiotherapy (CRT) and continued as maintenance (17 total q3w cycles) in the randomized, double-blind Phase 3 KEYNOTE-412 trial (NCT03040999); this post hoc subgroup focuses on PD-L1 CPS≥10 unresected, high-risk locally advanced HNSCC. In the CPS≥10 population (n=382; pembrolizumab n=194 vs placebo n=188) at the August 21, 2024 cutoff with 74.1 months median follow-up, median EFS was NR vs 61.4 months (HR 0.71, 95% CI 0.53-0.97) with 60-month EFS 62.4% vs 50.3%; OS was NR in both arms with 60-month OS 70.7% vs 60.9% (HR 0.75, 95% CI 0.53-1.04). Against current SOC (definitive cisplatin-RT), these 5-year survival/EFS rates sit in the expected long-term outcome range for CRT in mixed-risk populations, but the absolute ~12% higher 5-year EFS and ~10% higher 5-year OS here suggest enrichment by PD-L1 CPS≥10 may identify a subset where adding PD-1 meaningfully shifts the curve despite the overall KEYNOTE-412 being statistically negative at its prespecified threshold.