Background & aimsThe NAPOLI 3 trial demonstrated that compared to the nab-paclitaxel and gemcitabine (GemNab) regimen, the NALIRIFOX (5-fluorouracil, leucovorin, liposomal irinotecan, oxaliplatin) regimen can significantly improve patients' overall survival (OS) and progression-free survival (PFS), and the safety of this regimen is generally controllable. To ensure the appropriateness of the chosen treatment, economic evaluation is essential. Thus, from the perspective of American healthcare systems, we explored the cost-effectiveness comparison between NALIRIFOX or GemNab in treating patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) who had not previously received treatment.MethodsA three-state partitioned survival model was developed, incorporating a lifetime horizon with a 4-week cycle length. The efficacy data were sourced from the NAPOLI 3 study, while treatment costs, health state utilities, and adverse events (AEs) were obtained from public databases and literature. Applying an annual discount rate of 3%, the analysis focused on total cost, quality-adjusted life-years (QALYs), and the incremental cost-effectiveness ratio (ICER) as primary outcomes. Conducted within a US healthcare system perspective over a 13-year lifetime horizon, the analysis set willingness-to-pay (WTP) thresholds of $50,000, $100,000 and $150,000 per QALY. Sensitivity analyses were performed to assess the robustness of the model's findings.ResultsIn our base-case analysis, NALIRIFOX group was estimated to achieve an incremental gain of 0.13 QALYs. Compared to the GemNab group, treatment with NALIRIFOX resulted in higher costs ($150,437 vs $130,683). The ICER for NALIRIFOX therapy was calculated to be $155,602.83/QALYs. Sensitivity analysis revealed the model's robustness across a range of parameters. Through probabilistic sensitivity analysis applying Monte Carlo simulation with 1000 iterations, NALIRIFOX therapy was identified as the cost-effective regimen in 45.7% of all iterations at a WTP threshold of $150,000/QALYs.ConclusionsTreatment with NALIRIFOX strategy was estimated to provide a significant clinical advantage over GemNab. According to the model outcomes, NALIRIFOX therapy is borderline cost-effective for treatment-naive patients with mPDAC, slightly exceeding the highest conventional US willingness-to-pay threshold of 150,000/QALY. However, at lower thresholds, such as 100,000/QALY, NALIRIFOX fails to demonstrate cost-effectiveness in all simulations. In addition, NALIRIFOX therapy emerges as a cost-effective treatment strategy at higher willingness-to-pay thresholds or when the drug price is significantly reduced.