Economic evaluation of perioperative pembrolizumab plus standard of care as treatment for resectable locally advanced head and neck squamous cell carcinoma in the United States.

17 Background: In the phase 3 KEYNOTE-689 trial (NCT03765918) among patients with resectable stage III-IVA locally advanced head and neck squamous cell carcinoma (LA HNSCC), perioperative pembrolizumab (pembrolizumab before surgery [neoadjuvant], then continued in combination with standard-of-care [SOC] radiotherapy with or without cisplatin after surgery followed by pembrolizumab alone [adjuvant]) significantly prolonged event-free survival (EFS) vs. SOC alone, both in the intention-to-treat (ITT) population and PD-L1 combined positive score (CPS) ≥1 subgroup. This study evaluated the cost-effectiveness of perioperative pembrolizumab plus SOC vs. SOC for resectable LA HNSCC, from a United States healthcare payer perspective. Methods: A Markov cohort model with four states (event-free [EF], local recurrence [LR], incurable recurrence/progression [IRP], death) was developed to estimate lifetime costs, life years (LYs), and quality-adjusted LYs (QALYs) with 3% annual discounting. Transition probabilities were fitted to patient-level time-to-event data from KEYNOTE-689 through parametric multistate modeling to account for competing risks. Costs of initial and subsequent treatment, adverse events (AE), disease management, and terminal care were estimated in 2025$ based on trial results, drug labels, public databases, and literature. Utilities and AE disutilities were derived through analyses of EQ-5D-5L data collected in KEYNOTE-689. Sensitivity analyses were performed. Results: In the overall (ITT) population, incremental cost-effectiveness ratios (ICERs) of perioperative pembrolizumab plus SOC vs. SOC were $77,936/QALY and $64,745/LY (Table). In the CPS ≥1 subgroup, ICERs were $55,863/QALY and $46,406/LY. Higher initial treatment costs of perioperative pembrolizumab (incurred mainly in Year 1) were partly offset by lower LR/IRP-related costs in this arm. At the typical threshold of $150,000/QALY, perioperative pembrolizumab was cost-effective in 83% and 96% of probabilistic simulations in the overall (ITT) and CPS ≥1 populations, respectively. Conclusions: Perioperative pembrolizumab plus SOC was cost-effective relative to SOC for the treatment of resectable LA HNSCC in both ITT and CPS ≥1 populations. Clinical trial information: NCT03765918 . Outcomes Overall (ITT): Pembrolizumab + SOC Overall (ITT): SOC PD-L1 CPS ≥1: Pembrolizumab + SOC PD-L1 CPS ≥1: SOC Total cost (2025$) 204,131 117,009 201,679 119,368 Initial treatment cost in EF state 162,133 50,546 162,273 50,671 Subsequent treatment cost in LR/IRP states 14,260 38,703 11,723 40,939 AE and disease management cost in EF state 11,411 10,307 11,585 10,091 Disease management cost in LR/IRP states and terminal care cost 16,327 17,454 16,099 17,667 Total QALYs 6.94 5.82 7.12 5.65 Total LYs 8.55 7.21 8.77 7.00 ICER (Δ$/ΔQALYs) - 77,936 - 55,863 ICER (Δ$/ΔLYs) - 64,745 - 46,406