Systematic review and network meta-analysis of lorlatinib with comparison to other anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) as first-line treatment for ALK-positive advanced non-smallcell lung cancer (NSCLC)

IF 4.5 2区医学 Q1 ONCOLOGY

Lung Cancer Pub Date : 2024-09-29 DOI:10.1016/j.lungcan.2024.107968

Sai-Hong Ou , Hannah Kilvert , Jane Candlish , Ben Lee , Anna Polli , Despina Thomaidou , Hannah Le

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引用次数: 0

Abstract

Background

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).

Methods

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.

Results

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.

Conclusions

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.

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罗拉替尼与其他无性淋巴瘤激酶（ALK）酪氨酸激酶抑制剂（TKIs）作为ALK阳性晚期非小细胞肺癌（NSCLC）一线治疗药物的系统综述和网络荟萃分析。

背景：新一代无性淋巴瘤激酶（ALK）酪氨酸激酶抑制剂（TKIs）（阿来替尼、布瑞加替尼和lorlatinib）在一线（1L）治疗ALK阳性晚期非小细胞肺癌（NSCLC）中显示出优于化疗或克唑替尼的无进展生存期（PFS）：我们进行了网络荟萃分析（NMAs），比较了lorlatinib与其他ALK TKIs在该适应症中的相对疗效。从系统文献综述和后续更新中发现的证据构成了我们的证据基础。主要分析由独立审查委员会（IRC）对意向治疗（ITT）人群的PFS进行调查。次要结果包括亚组间的 PFS、颅内进展时间（IC TTP）、不良事件以及因不良事件而停药。对于每种结果，贝叶斯比例危险度近似模型都估算了相对治疗效果。此外，我们还比较了迄今为止已发表的8项针对1L ALK +晚期NSCLC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，允许进行间接治疗比较。两项试验直接比较了阿来替尼（600 毫克，每天两次）和克唑替尼，一项试验直接比较了洛拉替尼和克唑替尼。NMA结果显示，在将洛拉替尼与阿来替尼（600毫克，每天两次）进行比较时，ITT PFS IRC的危险比（95%可信区间[CrI]）为0.61（95% CrI：0.39，0.97）；在将洛拉替尼与布瑞替尼进行比较时，ITT PFS IRC的危险比为0.57（95% CrI：0.35，0.93）。在对已发表的NMA进行回顾时，比较了洛拉替尼与阿来替尼（600毫克，每天两次）和布加替尼的HRs。这一比较证实，每个已发表的NMA都得出了相似的结果：我们的NMA分析补充了现有的研究结果，并补充了其他已发表NMA的数据缺口。与其他TKIs相比，8项已发表的NMA研究结果一致支持罗拉替尼作为ALK+晚期NSCLC患者临床有效的1L治疗药物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Lung Cancer 医学-呼吸系统

CiteScore

9.40

自引率

3.80%

发文量

407

审稿时长

25 days

期刊介绍： Lung Cancer is an international publication covering the clinical, translational and basic science of malignancies of the lung and chest region.Original research articles, early reports, review articles, editorials and correspondence covering the prevention, epidemiology and etiology, basic biology, pathology, clinical assessment, surgery, chemotherapy, radiotherapy, combined treatment modalities, other treatment modalities and outcomes of lung cancer are welcome.