Pembrolizumab (PD-1) boosts peri-operative EFS in resectable head-and-neck SCC by ~21 mo

In the Phase 3 KEYNOTE-689 study (NCT03765918), 714 adults with stage III–IVA, resectable HNSCC were randomised to two neoadjuvant cycles, three concurrent cycles (during PORT), and 12 adjuvant cycles of pembrolizumab, a PD-1 inhibitor, (200 mg Q3W) plus surgery ± cisplatin-based radiotherapy vs SOC alone. At 38 mo median follow-up, median event-free survival improved to 51.8 mo vs 30.4 mo in the all-comer population and to 59.7 mo vs 26.9 mo in PD-L1 CPS ≥ 10 tumors. Major pathologic response differences favoured pembrolizumab by 9–14 percentage points. Grade ≥3 treatment-related AEs were comparable (44.6% vs 42.9%); immune-mediated events (chiefly hypothyroidism) occurred in 43% of pembro patients, with 4 vs 1 treatment-related deaths.