重要性：在开放标签的III期POSEIDON随机对照试验（RCT）中，局限的一段时间富雷米单抗加杜瓦利单抗和化疗（T + D + CT）在转移性非小细胞肺癌（mNSCLC）的一线治疗中，相较于化疗（CT），进展生存期（PFS）和总体生存期（OS）得以显著提高，而相对于化疗并无明显的额外耐受负担。然而，考虑到T + D + CT的高成本，其价值需要从效力和成本两个方面进行评估。 目标：从美国支付者的角度评估T + D + CT相对于CT的成本效益，用于未经治疗的mNSCLC患者。设计，环境和参与者：采用三状态Markov模型，根据POSEIDON三期RCT的结果，衡量T + D + CT相对于CT在一线mNSCLC治疗中的终身成本和效果，涉及675名mNSCLC患者。在分析中，模拟患者接受T + D + CT（最多四个21天周期），然后每4周注射一次杜瓦利单抗，直至疾病进展或无法接受的毒副作用，并额外注射一剂富雷米单抗，或者接受CT（最多六个21天周期，包括或不包括培美曲塞维持治疗；所有组别）。主要结果和测量：在愿意支付（WTP）每QALY 10万至15万美元的阈值下，评估了终身成本、基于质量调整的生存年（QALYs）和增量成本效益比（ICER）。通过一元和概率敏感性分析来调查模型的不确定性。结果：相较于CT，T + D + CT产生额外的0.36个QALYs，附加成本为217,694美元，导致ICER为608,667.86美元/QALY。一元敏感性分析显示，结果对杜瓦利单抗的成本最为敏感。其他具有较大或中度影响的变量包括无进展生存期的效用、进展期疾病状态的效用以及富雷米单抗的成本。概率敏感性分析表明，在WTP每QALY 10万至15万美元的阈值下，T + D + CT在mNSCLC患者中的成本效益概率为0%。 结论和相关性：在这个模型中，相对于CT，T + D + CT在WTP每QALY 10万至15万美元的阈值下被估计为不那么经济。当新的具有显著效果的联合治疗在一线治疗中成为重要时，为了实现未来可能的成本效益，可能需要降低杜瓦利单抗和富雷米单抗的价格。版权所有 © 2023 Liu，Huo和Chen。

Importance: In the open-label phase III POSEIDON randomized clinical trial (RCT), a limited course of tremelimumab plus durvalumab and chemotherapy (T + D + CT) indicated in the first-line treatment of metastatic non-small cell lung cancer (mNSCLC), progression-free survival, and overall survival (OS) were substantially improved without significant additional tolerance burden compared to chemotherapy (CT). However, given the high cost of T + D + CT, its value needs to be evaluated in terms of both potency and cost. Objective: To evaluate the cost-effectiveness of T + D + CT versus CT in individuals with previously untreated mNSCLC from a U.S. payer perspective. Design, setting, and participants: A three-state Markov model was adopted to weigh the lifetime costs and effectiveness of T + D + CT versus CT for the treatment of first-line mNSCLC, according to the results of the POSEIDON phase III RCT involving 675 individuals with mNSCLC. Individuals were simulated to undergo either T + D + CT for up to four 21-day cycles, followed by durvalumab once every 4 weeks until disease progression or unacceptable toxic effects and one additional tremelimumab dose, or CT for up to six 21-day cycles (with or without pemetrexed maintenance; all groups) in the analysis. Main outcomes and measures: Lifetime costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER) were evaluated with a willingness-to-pay (WTP) threshold of $ 100,000 to $ 150,000 per QALY. The uncertainty of the model was investigated using univariate and probabilistic sensitivity analysis. Results: T + D + CT produced additional 0.36 QALYs with additional costs of $ 217,694, compared to CT, giving rise to ICERs of $ 608,667.86/QALY. The univariate sensitivity analysis demonstrated that the outcomes were most sensitive to the cost of durvalumab. Other variables with a large or moderate influence were the utility of progression-free survival state, utility of progressive disease state, and cost of tremelimumab. Probability sensitivity analysis revealed that T + D + CT had a 0% probability of cost-effectiveness in individuals with mNSCLC at a willingness-to-pay threshold of $ 100,000 to $ 150,000 per QALY. Conclusion and relevance: In this model, T + D + CT was estimated to be less cost-effective than CT for patients with mNSCLC at a WTP threshold of $ 100,000 to $ 150,000 per QALY in the United States. When new combination therapies with remarkable effect become pivotal in the first-line treatment, the price reduction of durvalumab and tremelimumab may be necessary to achieve cost-effectiveness in future possible context.Copyright © 2023 Liu, Huo and Chen.