Efficacy of ALK inhibitors on NSCLC brain metastases: A systematic review and pooled analysis of 21 studies

BackgroundPatients with anaplastic lymphoma kinase rearranged (ALK+) non-small cell lung cancer (NSCLC) have a higher risk of developing brain metastases (BMs) than patients with other NSCLC sub-types. ALK inhibitors have activity in BMs due to ALK+ NSCLC. We performed a systematic review of the literature with the aim of assessing the efficacy of ALK inhibitors on BMs.Material and methodsA systematic search of the literature was performed using the databases Pubmed, EMBASE, Web of Science, The Cochrane Library, and SCOPUS. Relevant publications reporting activity of ALK inhibitors in NSCLC BMs were retrieved. Data were pooled using the number of events/number of evaluable patients according to fixed or random effect models. Intracranial tumour response was assessed through overall response rate (ORR), disease control rate (DCR: ORR + stable disease rate), median progression-free survival (PFS), and overall survival (OS). The primary endpoint was intracranial overall response rate (IC ORR).ResultsA total of 1,016 patients with BMs from 21 studies were analysed. In patients receiving ALK inhibitors in the first line setting, the pooled IC ORR was 39.17% (95%CI 13.1–65.2%), while the pooled IC ORR observed in further lines was 44.2% (95%CI 33.3–55.1%). Intracranial disease control rate (IC DCR) was 70.3% and 78.2% in naïve and pre-treated patients, respectively. Patients who had not received brain radiation attained an IC ORR of 49.0%.ConclusionsBased on these data, ALK inhibitors are effective in both naive and pre-treated patients with similar IC ORR and IC DCR, irrespective of the line of therapy.研究背景：间变性淋巴瘤激酶重排（ALK+）非小细胞肺癌（NSCLC）患者发生脑转移（BMs）的风险高于其他非小细胞肺癌亚型患者。针对ALK+ NSCLC，ALK抑制剂对脑转移具有治疗活性。本研究开展系统文献综述，旨在评估ALK抑制剂对脑转移的治疗效果。 材料与方法：本研究通过PubMed、EMBASE、Web of Science、Cochrane图书馆及SCOPUS数据库进行系统文献检索，筛选并纳入报道ALK抑制剂治疗NSCLC脑转移疗效的相关文献。依据固定效应模型或随机效应模型，以事件数/可评估患者数进行数据合并。采用客观缓解率（ORR）、疾病控制率（DCR：ORR+疾病稳定率）、中位无进展生存期（PFS）及总生存期（OS）评估颅内肿瘤应答情况，本研究的主要终点为颅内客观缓解率（IC ORR）。 研究结果：本研究共纳入21项研究的1016例脑转移患者进行分析。一线接受ALK抑制剂治疗的患者，合并颅内客观缓解率为39.17%（95%CI：13.1%~65.2%）；后线接受ALK抑制剂治疗的患者，合并颅内客观缓解率为44.2%（95%CI：33.3%~55.1%）。初治患者与经治患者的颅内疾病控制率（IC DCR）分别为70.3%与78.2%。未接受过脑放疗的患者，其颅内客观缓解率为49.0%。 研究结论：基于本研究数据，无论治疗线数如何，ALK抑制剂对初治及经治脑转移患者均具有治疗效果，且二者的颅内客观缓解率与颅内疾病控制率相近。