Abstract
BACKGROUND: Immunotherapy combinations like Pembrolizumab + Axitinib and Nivolumab + Ipilimumab have survival benefits over Sunitinib in advanced renal cell carcinoma (aRCC) first-line treatment. But their cost-effectiveness in the USA and China is unclear. OBJECTIVES: To assess the cost-effectiveness of three first-line treatment regimens for untreated aRCC-Nivolumab plus Ipilimumab, Pembrolizumab plus Axitinib, and Sunitinib-from the perspective of national health service systems and indirect healthcare payers in China and the USA, with a focus on intent-to-treat (ITT) populations and International mRCC Database Consortium (IMDC) risk stratifications. DESIGN: Decision-tree and Markov models, based on KEYNOTE-426 and CheckMate 214 trials, simulated 5-year disease progression of eligible patients. METHODS: The model, constructed using TreeAge Pro 2022 (TreeAge Software, LLC, Williamstown, Massachusetts, USA), incorporated three health states: progression-free survival, progressive disease, and death. Economic parameters included direct medical costs (first-line and second-line treatments, adverse event management, monitoring), quality-adjusted life year (QALYs), and incremental cost-effectiveness ratios (ICERs). Probabilistic sensitivity analysis was performed to evaluate model uncertainty. RESULTS: Across favorable-risk, intermediate/poor-risk IMDC subgroups, and the ITT population, Nivolumab plus Ipilimumab sequential Cabozantinib demonstrated the optimal cost-effectiveness in both countries, with ICERs below the willingness-to-pay (WTP) thresholds. It was associated with lower costs and higher QALYs compared to the other two regimens. Pembrolizumab plus Axitinib sequential Cabozantinib was more cost-effective than sunitinib sequential Cabozantinib in both regions, with ICERs also below WTP thresholds. CONCLUSION: In China and the USA, Nivolumab plus Ipilimumab is the most cost-effective first-line treatment for aRCC across different IMDC subgroups and the ITT population, followed by Pembrolizumab plus Axitinib, which outperforms sunitinib. These findings can guide clinical decision-making, though their generalizability is limited to China and the USA due to regional differences in drug pricing, payment systems, and market access.