晚期非小细胞肺癌与ALK融合的一线治疗：一项网状Meta分析。
Front-line treatment for advanced non-small-cell lung cancer and ALK fusion: a network meta-analysis.
作者信息
Wen Yaokai, Jiang Tao, Wu Xiangrong, Peng Haoxin, Ren Shengxiang, Zhou Caicun
机构信息
Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University Medical School Cancer Institute, Tongji University School of Medicine, Shanghai, China.
Nanshan School, Guangzhou Medical University, Guangzhou, China.
出版信息
Ther Adv Med Oncol. 2022 Aug 22;14:17588359221116607. doi: 10.1177/17588359221116607. eCollection 2022.
BACKGROUND
It remains unknown what is the optimal front-line choice for advanced non-small-cell lung cancer (NSCLC) with anaplastic lymphoma kinase (ALK) fusion.
METHODS
We conducted a systematic review and network meta-analysis of randomized phase III clinical trials comparing two or more treatments as the front-line setting for patients with advanced ALK-positive NSCLC.
RESULTS
Nine phase III randomized clinical trials with 2367 patients were included. As to efficacy, lorlatinib had the most favorable progression-free survival [PFS; surface under the cumulative ranking curve (SUCRA) = 98.4%] in the first-line setting, with noticeable outcome benefits chemotherapy [hazard ratio (HR): 0.12; 95% confidence interval (CI): 0.08-0.19], crizotinib (HR: 0.28; 95% CI: 0.19-0.41), ceritinib (HR: 0.22; 95% CI: 0.13-0.37), and brigatinib (HR: 0.58; 95% CI: 0.35-0.96), as well as beneficial trends when compared with alectinib (HR: 0.66; 95% CI: 0.41-1.04) and ensartinib (HR: 0.62; 95% CI: 0.36-1.08). Meanwhile, alectinib showed the optimal overall survival (OS; SUCRA = 91.2%), with significant improvements over chemotherapy (HR: 0.47; 95% CI: 0.30-0.72) and crizotinib (HR: 0.58; 95% CI: 0.41-0.82). Similarly, brigatinib also displayed prolonged OS compared with crizotinib after adjustment for crossover by the marginal structural model (HR: 0.54; 95% CI: 0.31-0.92). In terms of safety, alectinib had the fewest grade 3-5 adverse events (SUCRA = 98.9%), with marked advantages crizotinib [odds ratio (OR): 0.67; 95% CI: 0.46-0.97], ceritinib (OR: 0.21; 95% CI: 0.10-0.43), brigatinib (OR: 0.37; 95% CI: 0.20-0.69), ensartinib (OR: 0.48; 95% CI: 0.27-0.89), and lorlatinib (OR: 0.30; 95% CI: 0.16-0.54).
CONCLUSIONS
Lorlatinib may have advantageous PFS compared with other agents but a greater risk of severe toxicity. Second-generation inhibitors, including alectinib, brigatinib, and ensartinib, provide major efficacy with less toxicity and remain appropriate regimens in the front-line setting.
背景
对于间变性淋巴瘤激酶（ALK）融合的晚期非小细胞肺癌（NSCLC），最佳一线治疗选择仍不明确。
方法
我们对随机III期临床试验进行了系统评价和网状Meta分析，比较了两种或更多种治疗作为晚期ALK阳性NSCLC患者的一线治疗方案。
结果
纳入了9项III期随机临床试验，共2367例患者。在疗效方面，洛拉替尼在一线治疗中具有最有利的无进展生存期[PFS；累积排名曲线下面积（SUCRA）=98.4%]，与化疗[风险比（HR）：0.12；95%置信区间（CI）：0.08 - 0.19]、克唑替尼（HR：0.28；95%CI：0.19 - 0.41）、色瑞替尼（HR：0.22；95%CI：0.13 - 0.37）和布加替尼（HR：0.58；95%CI：0.35 - 0.96）相比有显著的疗效优势，与阿来替尼（HR：0.66；95%CI：0.41 - 1.04）和恩沙替尼（HR：0.62；95%CI：0.36 - 1.08）相比也有有利趋势。同时，阿来替尼显示出最佳的总生存期（OS；SUCRA = 91.2%），与化疗（HR：0.47；95%CI：0.30 - 0.72）和克唑替尼（HR：0.58；95%CI：0.41 - 0.82）相比有显著改善。同样，在通过边际结构模型调整交叉后，布加替尼与克唑替尼相比也显示出OS延长（HR：0.54；95%CI：0.31 - 0.92）。在安全性方面，阿来替尼发生3 - 5级不良事件最少（SUCRA = 98.9%），与克唑替尼[优势比（OR）：0.67；95%CI：0.46 - 0.97]、色瑞替尼（OR：0.21；95%CI：0.10 - 0.43）、布加替尼（OR：0.37；95%CI：0.20 - 0.69）、恩沙替尼（OR：0.48；95%CI：0.27 - 0.89）和洛拉替尼（OR：0.30；95%CI：0.16 - 0.54）相比有明显优势。
结论
与其他药物相比，洛拉替尼可能具有有利的PFS，但严重毒性风险更高。包括阿来替尼、布加替尼和恩沙替尼在内的第二代抑制剂疗效显著且毒性较小，仍是一线治疗的合适方案。
Zotero 插件