Background <p>Platinum-resistant ovarian cancer (PROC) has a poor prognosis and limited treatments. Relacorilant plus nab-paclitaxel (RnP) shows clinical efficacy in Phase III trials, but its cost-effectiveness has not yet been evaluated. This study evaluated RnP versus nab-paclitaxel (nP) for PROC from the U.S. payers’ perspective.</p> Methods <p>A partitioned survival model (1-month cycle, 5-year time horizon) was utilized to assess the cost-effectiveness of the RnP regimen for PROC, and appropriate parametric functions were applied to fit survival curves and extrapolate 5 years of treatment. Critical clinical data were derived from the ROSELLA trial. Costs and utility values were obtained from U.S. public websites and published literature. The primary outcomes were total cost, quality-adjusted life-years (QALYs), and the incremental cost-effectiveness ratio (ICER), which was benchmarked against a willingness-to-pay (WTP) threshold of $150,000/QALY. A comprehensive appraisal of model robustness was conducted, encompassing both one-way sensitivity analysis and probabilistic sensitivity analyses (PSA), in addition to scenario analyses to probe the conditions for the regimen’s economic feasibility.</p> Results <p>Compared with the nP regimen, the RnP regimen incurred an additional treatment cost of $43,161 but gained an extra 0.27 QALYs in health benefits. Ultimately, the ICER was calculated to be $161,753/QALY, which exceeded the WTP threshold of $150,000/QALY. One-way sensitivity analysis demonstrated that the price of relacorilant had the greatest influence on results, with the PSA showing a 38.9% probability of the RnP regimen being cost-effective. The probabilities that the RnP regimen was cost-effective for PROC were 2.3%, 38.9%, and 82.4% at WTP thresholds of $100,000, $150,000, and $200,000/QALY, respectively. Scenario analyses identified a definitive price threshold for relacorilant ($2.262/mg), representing a 7.8% reduction from the current estimated cost, at which the RnP regimen achieves cost-effectiveness. Subgroup analyses found that the RnP regimen was associated with a relative cost-effective outcome in several subgroups: those aged &gt; 65 years, patients with a primary platinum-free treatment interval ≤ 6 months, and patients with a taxane-free interval ≤ 6 months.</p> Conclusion <p>From the U.S. payers’ perspective, the RnP regimen is not cost-effective compared with the nP regimen for patients with PROC. Setting relacorilant’s price at $2.262/mg could render the RnP regimen cost-effective.</p>