{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T06:55:25Z","timestamp":1790751325391,"version":"4.1.0"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"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. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study aimed to systematically evaluate the efficacy of first-line immune checkpoint inhibitors (ICIs) combined with targeted therapy for advanced renal cell carcinoma (RCC) and assess their cost-effectiveness 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>Phase III randomized controlled trials comparing ICI-targeted combinations versus sunitinib as first-line treatment for advanced RCC were identified through systematic searches of PubMed, EMBASE, and the Cochrane Library. A network meta-analysis (NMA) was performed to compare the hazard ratios (HRs) for progression-free survival (PFS) and overall survival (OS) among different regimens. The surface under the cumulative ranking curve (SUCRA) was calculated to rank treatment efficacy. Based on the NMA results, a partitioned survival model was developed for the cost-effectiveness analysis. Using the sunitinib arm from the CheckMate 9ER trial as the reference, parametric survival models were fitted to extrapolate survival outcomes over a 20-year time horizon. HRs from the NMA were applied to derive survival curves for other interventions. The model cycle length was 6 weeks. Costs included drug acquisition, follow-up, adverse event management, subsequent therapy, and palliative care. Utility values were sourced from published literature. An incremental cost-effectiveness ratio (ICER) was calculated against a willingness-to-pay (WTP) threshold of $40,332.35 per quality-adjusted life-year (QALY). Sensitivity and scenario analyses were conducted.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Seven trials involving 4,973 patients were included. The NMA showed that pembrolizumab plus lenvatinib ranked highest for PFS, whereas toripalimab plus axitinib ranked highest for OS. The cost-effectiveness analysis indicated that toripalimab plus axitinib yielded the greatest gains in life-years and QALYs, with the lowest ICER of $62,204.37 among all evaluated strategies. However, all regimens exceeded the WTP threshold of $40,332.35 per QALY. Sensitivity analyses confirmed the robustness of these findings.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study demonstrates that while toripalimab plus axitinib is the most efficacious first-line regimen for aRCC and offers the lowest ICER, none of the evaluated regimens are economically viable from the perspective of the Chinese healthcare system at the WTP threshold of $40,332.35 per QALY.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Systematic review registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link>https:\/\/www.crd.york.ac.uk\/PROSPERO\/view\/CRD420261503119<\/jats:ext-link>\n                      , identifier CRD420261503119.\n                    <\/jats:p>\n                  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