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It is not known whether these immunotherapy agents are cost-effective for recurrent or metastatic squamous cell carcinomas of the head and neck (R\/M SCCHN). The purpose of this study was to compare the cost-effectiveness of nivolumab plus ipilimumab with EXTREME in the first-line setting from the standpoint of third-party payers in the United States. The projecting of costs and outcomes over 15\u00a0years was done using a three-state partitioned survival model discounted by 3% per year. Long-term extrapolation of CheckMate 651 was used to model progression-free\u00a0survival and overall survival\u00a0(OS). The incremental net health benefit (INHB), incremental net monetary benefit (INMB), quality-adjusted life\u00a0years (QALYs), and incremental cost-effectiveness ratio (ICER) were calculated. The uncertainty and stability of the model were accounted for via one-way and probabilistic sensitivity analyses. As compared with nivolumab plus ipilimumab, EXTREME was associated with an increase of 0.154 life-years and 0.076 QALYs, as well as a cost increase of $572 per patient. The corresponding ICERs were $7545\/QALY along with the values of INMB and INHB were $113,267 and 0.076 QALYs, respectively, at a willingness to pay (WTP) threshold of $150,000\/QALY. The probability of nivolumab plus ipilimumab being cost-effective was &gt;\u200999% in patients with combined positive score (CPS) \u2265\u20091, CPS 1\u201319, or CPS \u2265\u200920. Moreover, hazard ratio for OS and body weight were the most sensitive parameters for the model. According to sensitivity analyses, these results were generally robust. In overall populations with R\/M SCCHN, the EXTREME regimen is cost-effective compared with nivolumab plus ipilimumab. Given a WTP threshold of $150,000 per QALY, the probability of the EXTREME regiment being cost-effective compared with nivolumab and ipilimumab, was 64%. Importantly, there was heterogeneity in the cost-effectiveness probabilities, based on primary sites and expression levels of PD-L1. Therefore, tailored treatment based on individual patient and clinical characteristics, remains important, and may impact the cost-effectiveness of the regimens under study.<\/jats:p>","DOI":"10.1038\/s41598-024-57277-7","type":"journal-article","created":{"date-parts":[[2024,3,21]],"date-time":"2024-03-21T08:02:11Z","timestamp":1711008131000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Nivolumab plus ipilimumab versus the EXTREME regimen in recurrent\/metastatic squamous cell carcinoma of the head and neck: a cost-effectiveness analysis"],"prefix":"10.1038","volume":"14","author":[{"given":"Dongmei","family":"Ye","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueyan","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyu","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,3,21]]},"reference":[{"key":"57277_CR1","doi-asserted-by":"publisher","first-page":"954","DOI":"10.1080\/13696998.2022.2095826","volume":"25","author":"RH Borse","year":"2022","unstructured":"Borse, R. 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