{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T15:51:59Z","timestamp":1791474719945,"version":"4.3.4"},"reference-count":29,"publisher":"American Medical Association (AMA)","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Otolaryngol Head Neck Surg"],"published-print":{"date-parts":[[2026,10,1]]},"abstract":"<jats:sec id=\"ab-ooi260044-4\">\n                    <jats:title>Importance<\/jats:title>\n                    <jats:p>The KEYNOTE-689 trial demonstrated improved event-free survival with the addition of perioperative pembrolizumab to standard of care for patients with locally advanced head and neck squamous cell carcinoma (HNSCC), yet the cost-effectiveness remains unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-ooi260044-5\">\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To evaluate the cost-effectiveness of the KEYNOTE-689 perioperative pembrolizumab protocol.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-ooi260044-6\">\n                    <jats:title>Design, Setting, and Participants<\/jats:title>\n                    <jats:p>A partitioned survival model simulated the KEYNOTE-689 trial cohort with 3 mutually exclusive health states: event-free survival, disease progression, and death. Model inputs included Healthcare Cost and Utilization Project\u2013derived and US Centers for Medicare &amp;amp;amp; Medicaid Services\u2013derived costs for drug acquisition (pembrolizumab and cisplatin), administration, surgery, radiation therapy, supportive care, management of serious adverse events, and disease progression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-ooi260044-7\">\n                    <jats:title>Main Outcome and Measures<\/jats:title>\n                    <jats:p>KEYNOTE-689 Kaplan-Meier survival estimates were digitized and data for the combined positive score (CPS) of 1 to 10 subgroup were derived from the reported CPS of 1 or greater and CPS of 10 or greater subgroups. Quality-adjusted life-year (QALY) values for different health states were sourced from published literature, with the US population preference-weighting algorithm applied to EuroQol 5-Dimension 3-Level health questionnaire data from the CheckMate 141 trial. The primary outcome was the incremental cost-effectiveness ratio (ICER) results stratified by programmed cell death 1 ligand 1 (PD-L1) combined positive score (CPS of 1 to 10 vs greater than 10). A probabilistic sensitivity analysis (PSA) was performed to evaluate parameter uncertainty.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-ooi260044-8\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Subgroup analyses based on PD-L1 expression yielded divergent results. In the CPS greater than 10 cohort, perioperative pembrolizumab was cost-effective, producing approximately 1.35 additional QALYs at an incremental cost of $181\u202f900, resulting in an ICER of $134\u202f700. PSA showed a 57% probability that the pembrolizumab strategy was cost-effective at a $150\u202f000 willingness-to-pay (WTP) threshold. In the CPS of 1 to 10 cohort, perioperative pembrolizumab resulted in approximately 0.08 additional QALYs at an incremental cost of $166\u202f500, for an ICER of $2\u202f179\u202f400, with the PSA demonstrating an 11% probability of cost-effectiveness at a $150\u202f000 WTP threshold.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-ooi260044-9\">\n                    <jats:title>Conclusions and Relevance<\/jats:title>\n                    <jats:p>In this economic evaluation, addition of perioperative pembrolizumab to standard treatment for locally advanced HNSCC may represent a cost-effective intervention for patients with a PD-L1 CPS greater than 10 if KEYNOTE-689 data are replicable in clinical practice. Perioperative pembrolizumab is not a cost-effective strategy for patients with a CPS less than 10 based on current data. Biomarker stratification may inform the value-based integration of immunotherapy among patients with HNSCC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1001\/jamaoto.2026.2124","type":"journal-article","created":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T15:30:22Z","timestamp":1786030222000},"page":"927","source":"Crossref","is-referenced-by-count":1,"title":["Combined Positive Score and Cost-Effectiveness of Perioperative Pembrolizumab for Head and Neck Cancer"],"prefix":"10.1001","volume":"152","author":[{"given":"Aidan H.","family":"Coyle","sequence":"first","affiliation":[{"name":"Department of Health Management and Policy, School of Public Health, University of Michigan, Ann Arbor"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David W.","family":"Hutton","sequence":"additional","affiliation":[{"name":"Department of Health Management and Policy, School of Public Health, University of Michigan, Ann Arbor"},{"name":"Department of Internal Medicine, 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