Cost-effectiveness of neoadjuvant/adjuvant pembrolizumab versus standard of care for locally advanced head and Neck squamous cell carcinoma in China and the United States

BACKGROUND: The KEYNOTE-689 trial demonstrated clinical benefits of perioperative pembrolizumab in locally advanced head and neck squamous cell carcinoma (LA-HNSCC), but its economic value remains uncertain. RESEARCH DESIGN AND METHODS: A partitioned survival model evaluated neoadjuvant/adjuvant pembrolizumab (two 200 mg neoadjuvant cycles and fifteen 200 mg adjuvant cycles every 3 weeks) plus standard of care (surgery and postoperative radiotherapy ± cisplatin) versus open-label standard of care alone over a 30-year horizon from Chinese and US payer perspectives. Efficacy, severe adverse events (AEs; grade ≥ 3 stomatitis, cytopenias), utilities, and direct medical costs (2025 USD) were synthesized. Subgroups were stratified by PD-L1 combined positive score (CPS). RESULTS: In the overall population, pembrolizumab was not cost-effective in either the US (ICER, $212,183.93/QALY) or China ($114,422.43/QALY). In the US, ICERs were $142,495.35/QALY for CPS ≥ 1 and $127,668.80/QALY for CPS ≥ 10, below the $150,000/QALY threshold, with cost-effectiveness probabilities of 57.5% and 49.2%, respectively. In China, all subgroup ICERs exceeded the $40,334/QALY threshold. CONCLUSIONS: Perioperative pembrolizumab may offer economic value for selected US patients with PD-L1 CPS ≥ 1 or ≥10, although substantial decision uncertainty remains. It was not cost-effective in China or in the overall population under current pricing.