本研究的目的是评估洛美替尼相对于阿来替尼和布里加替尼，在西班牙未经治疗的ALK阳性晚期非小细胞肺癌患者的疗效。我们构建了一个分割的生存模型，包括无进展、非颅内进展、颅内进展和死亡健康状态，用于估计一生中累积的总成本、获得的生命年和经过质量调整的生命年。洛美替尼的总生存(OS)和无进展生存(PFS)来源于CROWN研究。针对阿来替尼和布里加替尼，我们进行了一项基于随机对照试验的网络荟萃分析，以估计它们与克唑替尼的OS和PFS风险比。效用是基于CROWN（洛美替尼）、ALEX（阿来替尼）和ALTA-1L（布里加替尼）研究中的EQ-5D-5L数据进行估计的。根据西班牙国家卫生体系的观点，总成本（以2021年的欧元表示）包括药物采购和随后的治疗、ALK+晚期非小细胞肺癌治疗和不良事件管理以及姑息治疗。单元成本来自本地成本数据库和文献。成本、生命年和经过质量调整的生命年以每年3%的折旧率计算。确定性和概率敏感性分析用于测试模型的稳健性。洛美替尼相比于阿来替尼提供了更高的健康结果（每患者+0.70个生命年增益，+1.42个经过质量调整的生命年增益）和更低的成本（每患者-9239欧元）。洛美替尼相对于布里加替尼获得了更高的生命年增益（+1.74）和经过质量调整的生命年增益（+2.30），但成本更高（每患者+36,627欧元），结果为每获得一个经过质量调整的生命年的增益所需的增量成本-效果比为15,912欧元。本研究的结果提示，洛美替尼可能是相对于阿来替尼的优势治疗选择。对于每获得一个经过质量调整的生命年的意愿支付门槛为25,000欧元/经过质量调整的生命年，洛美替尼可能是与布里加替尼相比的有效选择。© 2023 Presa et al.

The objective of the present study was to evaluate the efficiency of lorlatinib compared to alectinib and brigatinib for the treatment of adult patients with anaplastic lymphoma kinase (ALK)-positive advanced non-small cell lung cancer (NSCLC) previously not treated, in Spain.A partitioned survival model comprised progression free, non-intracranial progression, intracranial progression, and death health states was constructed to estimate the total costs, life-years gained (LYG) and quality-adjusted life years (QALYs) accumulated in a lifetime horizon. Overall survival (OS) and progression-free survival (PFS) for lorlatinib were obtained from the CROWN study. For alectinib and brigatinib, a network meta-analysis of randomized controlled trials was conducted to estimate OS and PFS hazard ratios versus crizotinib. Utilities were estimated based on EQ-5D-5L data derived from the CROWN (lorlatinib), ALEX (alectinib) and ALTA-1L (brigatinib) studies. According to the Spanish National Health Service perspective the total costs (expressed in euros using a 2021 cost year) included drug acquisition and the administration's subsequent treatment, ALK+ advanced NSCLC management and adverse-event management, and palliative care. Unitary costs were obtained from local cost databases and literature. Costs, LYGs and QALYs were discounted at 3% annually. Deterministic and probabilistic sensitivity analyses were used to test the model's robustness.Lorlatinib provided higher health outcomes (+0.70 LYG/patient, +1.42 QALYs/patient) and lower costs (-€9239/patient) than alectinib. Lorlatinib yielded higher LYG (+1.74) and QALYs (+2.30) versus brigatinib but higher costs/patient (+€36,627), resulting in an incremental-cost-effectiveness-ratio of €15,912/QALY gained.The results of this study suggest that lorlatinib may be a dominant treatment option versus alectinib. Considering a willingness-to-pay threshold of €25,000/QALY, lorlatinib may be an efficient option compared to brigatinib.© 2023 Presa et al.