Objective <p>The RENOTORCH trial found that toripalimab plus axitinib extended progression-free and overall survival in patients with advanced renal cell carcinoma (RCC), though its financial burden may limit widespread use. This study aimed to assess the cost-effectiveness of toripalimab plus axitinib compared with sunitinib monotherapy as a first-line therapy for patients with previously untreated or intermediate- or poor-risk advanced RCC from a US third-party payer perspective. </p> Methods <p>A three-state partitioned survival model (progression-free, progression, death) was utilized, with clinical outcomes obtained from the RENOTORCH trial. Progression-free survival (PFS) and overall survival (OS) were modeled using various parametric functions over a 5-year horizon, applying a 3% annual discount rate. Costs of treatments, administration, monitoring, and management of grade 3/4 adverse events (≥ 5% occurrence) were sourced from Micromedex® and Centers for Medicare &amp; Medicaid Services (CMS) databases. Life years (LY), quality-adjusted life years (QALY), and incremental costs per LY and QALY were estimated. One-way and probabilistic sensitivity analyses were conducted. Subgroup analyses for intermediate- and poor-risk patients, as classified by the International Metastatic RCC Database Consortium (IMDC) criteria, were performed using similar methods.</p> Results <p>Toripalimab plus axitinib increased total costs by $332,359, gained 0.68 LY and 0.36 QALY compared with sunitinib, resulting in incremental costs of $489,747 per LY and $923,962 per QALY. One-way sensitivity analysis showed that the incremental cost per QALY was most sensitive to changes in toripalimab plus axitinib’s cost. At a $150,000 willingness-to-pay threshold, probabilistic sensitivity analysis showed a nearly 0% probability of toripalimab plus axitinib being cost-effective. Similarly, toripalimab plus axitinib was still not cost-effective for intermediate- and poor-risk patients.</p> Conclusions <p>Compared with sunitinib monotherapy, our study suggested that toripalimab plus axitinib was not cost-effective for patients with advanced renal cell carcinoma from a US third-party payer perspective. Further analyses are warranted when more data are available.</p> <p>Despite benefits across different risk groups, toripalimab plus axitinib was not cost-effective for intermediate- and poor-risk patients.</p>