{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T05:47:05Z","timestamp":1782798425592,"version":"3.54.5"},"reference-count":27,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:00:00Z","timestamp":1782777600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Nivolumab plus ipilimumab has demonstrated survival benefits as first-line therapy for unresectable hepatocellular carcinoma (HCC). However, the high treatment cost may limit its economic value in China. This study evaluated the cost-effectiveness of nivolumab plus ipilimumab versus lenvatinib or sorafenib for unresectable HCC from the perspective of the Chinese healthcare system.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A partitioned survival model (PSM) with progression-free survival (PFS), progressed disease (PD), and death health states was developed over a 10-year time horizon. Clinical data were obtained from the phase III CheckMate 9DW trial. Overall survival (OS) and PFS data were reconstructed from published Kaplan\u2013Meier curves and extrapolated using alternative parametric and flexible survival models. Model selection was based on statistical fit, visual inspection, and clinical plausibility. Structural uncertainty was explored through 625 survival model combinations and multiple scenario analyses involving time horizons, post-progression treatment, treatment exposure, adverse event (AE) management, utility values, and non-drug medical costs. Threshold and price\u2013willingness-to-pay (WTP) analyses were conducted to evaluate the impact of treatment price reductions on cost-effectiveness outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In the base-case analysis, nivolumab plus ipilimumab increased total costs (USD 162,437.52 vs. USD 81,990.70) and quality-adjusted life years (QALYs) (1.89 vs. 1.40), resulting in an incremental cost-effectiveness ratio (ICER) of USD 164,177.18\/QALY, substantially exceeding the Chinese WTP threshold of USD 28,972.38\/QALY. Across all 625 survival model combinations and scenario analyses, ICERs consistently remained above the predefined WTP threshold. Scenario analyses demonstrated that the economic conclusions were generally robust to alternative assumptions regarding survival extrapolation, utility inputs, downstream treatment, treatment exposure, and healthcare costs. Price-threshold analyses indicated that an approximate 67% reduction in treatment cost would be required for nivolumab plus ipilimumab to reach the conventional Chinese WTP threshold.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>At current prices, nivolumab plus ipilimumab is unlikely to be cost-effective as a first-line treatment for unresectable HCC in China. This conclusion remained consistent across extensive structural and parameter uncertainty analyses. Substantial price reductions may be required to improve the economic value of dual immunotherapy in the Chinese healthcare setting.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1860312","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T05:41:04Z","timestamp":1782798064000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Cost-effectiveness of nivolumab plus ipilimumab versus lenvatinib or sorafenib for unresectable hepatocellular carcinoma in China: a modeling study with price threshold analysis"],"prefix":"10.3389","volume":"17","author":[{"given":"Rui","family":"Feng","sequence":"first","affiliation":[{"name":"School of Disaster and Emergency Medicine, Tianjin University","place":["Tianjin, China"]},{"name":"Department of Pharmacy, The Fourth Hospital of Hebei Medical University","place":["Shijiazhuang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liman","family":"Huo","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The Fourth Hospital of Hebei Medical University","place":["Shijiazhuang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun-Feng","family":"Diao","sequence":"additional","affiliation":[{"name":"Institute of Traumatic Brain Injury and Neurology, Characteristic Medical Center of PAPF","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yajing","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The Fourth Hospital of Hebei Medical University","place":["Shijiazhuang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The Fourth Hospital of Hebei Medical University","place":["Shijiazhuang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The Fourth Hospital of Hebei Medical University","place":["Shijiazhuang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Lv","sequence":"additional","affiliation":[{"name":"School of Disaster and Emergency Medicine, Tianjin University","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"722","DOI":"10.1177\/0272989X12458348","article-title":"Model parameter estimation and uncertainty analysis: a report of the ISPOR-SMDM modeling good research practices task force working Group-6","volume":"32","author":"Briggs","year":"2012","journal-title":"Med. 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