新一代间变性淋巴瘤激酶 (ALK) 酪氨酸激酶抑制剂 (TKI)（艾乐替尼、布加替尼和劳拉替尼）作为 ALK 阳性晚期非一线 (1L) 治疗的一线 (1L) 药物，表现出优于化疗或克唑替尼的无进展生存期 (PFS)。 -小细胞肺癌 (NSCLC)。我们进行了网络荟萃分析 (NMA)，比较了 lorlatinib 与其他 ALK TKI 在此适应症中的相对疗效。从系统的文献综述和随后的更新中确定的证据构成了我们证据的基础。主要分析由独立审查委员会 (IRC) 在意向治疗 (ITT) 人群中调查 PFS。次要结局包括亚组间的 PFS、颅内进展时间 (IC TTP)、不良事件以及因不良事件而停药。对于每个结果，贝叶斯比例风险 NMA 估计了相对治疗效果。此外，我们还比较了迄今为止针对 1L ALK 晚期 NSCLC 进行的八项已发表的 NMA 的设计和结果。我们形成了一个由 10 项试验组成的网络，可以进行间接治疗比较。两项试验直接比较了艾乐替尼（600 毫克，每日两次）与克唑替尼，一项试验直接比较了劳拉替尼与克唑替尼。 NMA 的结果表明，将 lorlatinib 与艾乐替尼（600 mg，每日两次）进行比较时，ITT PFS IRC 的风险比（95% 可信区间 [CrI]）分别为 0.61（95% CrI：0.39、0.97）和 0.57（95% CrI）。 CrI：0.35、0.93）当比较劳拉替尼和布加替尼时。在对已发表的 NMA 的审查中，比较了劳拉替尼与艾乐替尼（600 毫克，每天两次）和布加替尼的 HR。这一比较证实了每个已发布的 NMA 都产生了相似的结果。我们的 NMA 分析补充了现有的发现，并补充了其他已发布的 NMA 的数据差距。与其他 TKI 相比，八项已发表的 NMA 的研究结果一致支持 lorlatinib 作为 ALK 晚期 NSCLC 患者的临床有效 1L 治疗方法。版权所有 © 2024 作者。由 Elsevier B.V. 出版。保留所有权利。

Next-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) (alectinib, brigatinib, and lorlatinib) demonstrate superior progression-free survival (PFS) over chemotherapy or crizotinib as first-line (1L) treatment of ALK-positive advanced non-smallcell lung cancer (NSCLC).We conducted network meta-analyses (NMAs) comparing the relative efficacy of lorlatinib with other ALK TKIs in this indication. Evidence identified from a systematic literature review and subsequent updates formed the basis of our evidence. The primary analysis investigated PFS by independent review committee (IRC) in the intent-to-treat (ITT) population. Secondary outcomes included PFS among subgroups, intracranial time to progression (IC TTP), adverse events, and discontinuation due to adverse events. For each of the outcomes, Bayesian proportional hazards NMAs estimated the relative treatment effects. Additionally, we compared the design and results of eight published NMAs conducted for 1L ALK + advanced NSCLC to date.We formed a network of 10 trials, allowing indirect treatment comparisons. Two trials directly compared alectinib (600 mg twice daily) to crizotinib and one trial directly compared lorlatinib to crizotinib. The results of the NMA show that the hazard ratios (95 % credible interval [CrI]) for ITT PFS IRC were 0.61 (95 % CrI: 0.39, 0.97) when comparing lorlatinib with alectinib (600 mg twice daily) and 0.57 (95 % CrI: 0.35, 0.93) when comparing lorlatinib with brigatinib. In the review of published NMAs, HRs for lorlatinib versus alectinib (600 mg twice daily) and brigatinib were compared. This comparison confirmed that each published NMA yielded similar results.Our NMA analysis adds to existing findings and supplements data gaps from other published NMAs. Findings from eight published NMAs consistently supported lorlatinib as a clinically effective 1L treatment for ALK + advanced NSCLC patients compared to other TKIs.Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.