Liu Wenjie, Fang Yuting, Zhang Chao, Xiang Midan, Qi Lijuan, Su Aijiang, Sun Yongkun
National Clinical Research Center for Cancer/Cancer Hospital, National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Chaoyang District Panjiayuan Nanli No. 17, Beijing, 100021, China.
Department of Medical Oncology, Beijing Chaoyang District Sanhuan Cancer Hospital, Beijing, 100122, China.
BMC Gastroenterol. 2025 Apr 17;25(1):266. doi: 10.1186/s12876-025-03867-2.
BACKGROUND & AIMS: The 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.
A 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.
In 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.
Treatment 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.
NAPOLI 3试验表明，与白蛋白结合型紫杉醇和吉西他滨（GemNab）方案相比，NALIRIFOX（5-氟尿嘧啶、亚叶酸钙、脂质体伊立替康、奥沙利铂）方案可显著提高患者的总生存期（OS）和无进展生存期（PFS），且该方案的安全性总体可控。为确保所选治疗的合理性，经济评估至关重要。因此，从美国医疗保健系统的角度出发，我们探讨了NALIRIFOX与GemNab在治疗既往未接受过治疗的转移性胰腺导管腺癌（mPDAC）患者中的成本效益比较。
建立了一个三状态分区生存模型，纳入了为期4周的生命周期的终生视角。疗效数据来源于NAPOLI 3研究，而治疗成本、健康状态效用和不良事件（AE）则从公共数据库和文献中获取。采用3%的年贴现率，分析重点关注总成本、质量调整生命年（QALY）和增量成本效益比（ICER）作为主要结果。在13年的终生视角内，从美国医疗保健系统的角度进行分析，设定每QALY支付意愿（WTP）阈值为50,000美元、100,000美元和150,000美元。进行敏感性分析以评估模型结果的稳健性。
在我们的基础案例分析中，估计NALIRIFOX组可实现0.13 QALY的增量收益。与GemNab组相比，NALIRIFOX治疗导致成本更高（150,437美元对130,683美元）。NALIRIFOX治疗的ICER计算为155,602.83美元/QALY。敏感性分析揭示了模型在一系列参数范围内的稳健性。通过应用蒙特卡罗模拟进行1000次迭代的概率敏感性分析，在每QALY支付意愿阈值为150,000美元时，NALIRIFOX治疗在所有迭代中的45.7%被确定为具有成本效益的方案。
估计NALIRIFOX策略治疗比GemNab具有显著的临床优势。根据模型结果，NALIRIFOX治疗对于未接受过治疗的mPDAC患者在成本效益方面处于临界状态，略超过美国传统最高支付意愿阈值150,000美元/QALY。然而，在较低阈值下，如100,000美元/QALY，NALIRIFOX在所有模拟中均未显示出成本效益。此外，在较高的支付意愿阈值或药物价格大幅降低时，NALIRIFOX治疗成为一种具有成本效益的治疗策略。
