系统性综述与网络荟萃分析：lorlatinib作为一线治疗ALK阳性晚期非小细胞肺癌（NSCLC）与其他ALK酪氨酸激酶抑制剂（TKIs）比较
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)
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影响因子:4.4
分区:医学2区 / 肿瘤学3区 呼吸系统3区
发表日期:2024 Nov
作者:
Sai-Hong Ou, Hannah Kilvert, Jane Candlish, Ben Lee, Anna Polli, Despina Thomaidou, Hannah Le
DOI:
10.1016/j.lungcan.2024.107968
摘要
新一代间变性淋巴瘤激酶（ALK）酪氨酸激酶抑制剂（TKIs）（如alectinib、brigatinib和lorlatinib）在ALK阳性晚期非小细胞肺癌（NSCLC）的一线治疗中显示出优于化疗或crizotinib的无进展生存期（PFS）。我们进行了网络荟萃分析（NMA），比较lorlatinib与其他ALK TKI的相对疗效。系统文献回顾及后续更新所得的证据构成了本研究的基础。主要分析关注意向治疗（ITT）人群中的由独立评审委员会（IRC）评估的PFS。次要指标包括亚组中的PFS、颅内进展时间（IC TTP）、不良事件及因不良事件中断治疗的比例。每项指标均通过贝叶斯比例风险模型估算相对治疗效果。我们还对迄今为止发表的八个关于一线ALK阳性晚期NSCLC的NMA进行了比对，构建了一个包含10项试验的网络，进行间接治疗比较。其中两项试验直接比较alectinib（600 mg双剂量）与crizotinib，另一项试验直接比较lorlatinib与crizotinib。NMA结果显示，lorlatinib相较于alectinib（600 mg双剂量）和brigatinib的危险比（HR）（95%可信区间[CrI]）分别为0.61（CrI：0.39–0.97）和0.57（CrI：0.35–0.93）。对已发表的NMA进行回顾，发现lorlatinib相较于alectinib（600 mg双剂量）和brigatinib的HR值相似。这些分析结果支持lorlatinib作为一线治疗ALK阳性晚期NSCLC的有效性，弥补了其他研究中的数据空白，并得到了多项NMA的一致支持。
Abstract
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.