Departments of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, PR China; State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, PR China.
State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, PR China; Department of Thoracic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, PR China.
Pharmacol Res. 2021 Dec;174:105931. doi: 10.1016/j.phrs.2021.105931. Epub 2021 Oct 6.
More clinical evidence is needed regarding the ranking priority of interventions for ALK-positive, brain metastatic (BM) non-small cell lung cancer (NSCLC). Eligible randomized controlled trials (RCTs) were identified. Progression-free survival (PFS), objective response rate (ORR) and overall survival (OS) for the intended populations were analyzed with random effects, Bayesian network meta-analysis with the estimated hazard ratio (HR) and odds ratio (OR) with 95% credible interval (95% CrIs). We included 11 RCTs (2687 NSCLC and 991 BM patients) investigating 7 treatments and 5 medication classes. For PFS for BM patients, lorlatinib (hazard ratio (HR): 0.01, 95% CrI: 0.001-0.12), alectinib (HR: 0.05, 95% CrI: 0.01-0.21) and brigatinib (HR: 0.07, 95% CrI: 0.007-0.76) were top-ranking individual treatments; for ORR for BM patients, brigatinib, lorlatinib and alectinib were top-ranking treatments. For PFS for all NSCLC patients, the top-ranking individual treatments were lorlatinib (HR: 0.05, 95% CrI: 0.02-0.13), alectinib (HR: 0.09, 95% CrI: 0.05-0.18) and brigatinib (HR: 0.11, 95% CrI: 0.05-0.28). For OS for all NSCLC patients, we found that no individual treatments were superior to chemotherapy, whereas the following top-ranking interventions were alectinib (HR: 0.29, 95% CrI: 0.03-1.68), lorlatinib (HR: 0.41, 95% CrI: 0.04-4.13), and ceritinib (HR: 0.63, 95% CrI: 0.10-4.25). The results of individual treatments and medication classes were similar. Data were limited in regard to subgroup analyses and adverse events of BM patients. Lorlatinib has the most statistical superiority for BM patients, but ORR differences between third- and second-generation inhibitors are not obvious. All things considered, alectinib is recommended as first-line treatment, followed by lorlatinib, especially after developing drug resistance to alectinib.
需要更多的临床证据来确定 ALK 阳性、脑转移（BM）非小细胞肺癌（NSCLC）干预措施的优先排序。纳入了 11 项 RCT（2687 例 NSCLC 和 991 例 BM 患者），共涉及 7 种治疗方法和 5 种药物类别。对于 BM 患者的 PFS，洛拉替尼（HR：0.01，95%CrI：0.001-0.12）、阿来替尼（HR：0.05，95%CrI：0.01-0.21）和布加替尼（HR：0.07，95%CrI：0.007-0.76）是排名最高的个体治疗方法；对于 BM 患者的 ORR，布加替尼、洛拉替尼和阿来替尼是排名最高的治疗方法。对于所有 NSCLC 患者的 PFS，排名最高的个体治疗方法是洛拉替尼（HR：0.05，95%CrI：0.02-0.13）、阿来替尼（HR：0.09，95%CrI：0.05-0.18）和布加替尼（HR：0.11，95%CrI：0.05-0.28）。对于所有 NSCLC 患者的 OS，我们发现没有个体治疗方法优于化疗，而排名最高的干预措施包括阿来替尼（HR：0.29，95%CrI：0.03-1.68）、洛拉替尼（HR：0.41，95%CrI：0.04-4.13）和塞瑞替尼（HR：0.63，95%CrI：0.10-4.25）。个体治疗方法和药物类别的结果相似。对于 BM 患者的亚组分析和不良反应，数据有限。洛拉替尼对 BM 患者具有最大的统计学优势，但第三代和第二代抑制剂之间的 ORR 差异并不明显。综合考虑，阿来替尼被推荐为一线治疗药物，其次是洛拉替尼，尤其是在对阿来替尼产生耐药性后。
