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
Journal of Medical Economics, 2026
Aims
In the phase 3 KEYNOTE-689 trial (NCT03765918) among patients with resectable locally advanced head and neck squamous cell carcinoma (LA HNSCC), perioperative pembrolizumab (pembrolizumab before surgery, then continued with standard-of-care [SOC] radiotherapy +/- cisplatin after surgery followed by pembrolizumab alone) significantly prolonged event-free survival vs. SOC alone, both in the intention-to-treat population and PD-L1 combined positive score (CPS) ≥1 subgroup. Perioperative pembrolizumab + SOC received Food and Drug Administration approval in June 2025 for resectable LA HNSCC expressing PD-L1 (CPS ≥ 1). The present study evaluated the cost-effectiveness of perioperative pembrolizumab + SOC versus SOC in this indication, from a US healthcare payer perspective.
Materials and methods
A Markov cohort model with four states (event-free, local recurrence, incurable recurrence/progression, 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 modelling. Costs of initial and subsequent treatment, adverse events, disease management, and terminal care were estimated in 2025$ based on trial results, drug labels, public databases, and literature. Utilities were derived through analyses of EQ-5D-5L data collected in KEYNOTE-689. Deterministic and probabilistic sensitivity analyses were performed.
Results
Compared to SOC, perioperative pembrolizumab + SOC increased total costs by $82,311 and provided gains of 1.47 QALYs and 1.77 LYs. Incremental cost-effectiveness ratios of perioperative pembrolizumab + SOC vs. SOC were $55,863/QALY and $46,406/LY. Higher initial treatment costs of perioperative pembrolizumab (incurred mainly in Year 1) were partially offset by lower recurrence-related costs. At the typical $150,000/QALY threshold, perioperative pembrolizumab + SOC was cost-effective in 96% of probabilistic simulations.
Limitations
Survival extrapolations beyond the available trial period are subject to uncertainty.
Conclusions
Perioperative pembrolizumab + SOC was found to be cost-effective versus SOC for the treatment of resectable LA HNSCC with CPS ≥ 1.
Authors
Feng Q, Bensimon A, Tzontcheva A, Benjamin K, Uppaluri R, Adkins D, Johnson G, Fernan C, Zheng D, Tang Y, Chafamo B, Muston D