First-line immune checkpoint inhibitors combined with targeted therapy for advanced renal cell carcinoma: a network meta-analysis and cost-effectiveness analysis

Objective 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. Methods 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. Results 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. Conclusion 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. Systematic review registration https://www.crd.york.ac.uk/PROSPERO/view/CRD420261503119 , identifier CRD420261503119.