Anaplastic lymphoma kinase inhibitors in non-small cell lung cancer patients with brain metastases: a meta-analysis.

Abstract

Patients with anaplastic lymphoma kinase (ALK) rearrangements are particularly prone to development of brain metastases (BMs). Newer anti-ALK treatments have demonstrated far greater intracranial efficacy. Here we performed a meta-analysis with the aim of assessing the efficacy of ALK inhibitors on BMs. A search of published trials was conducted in PubMed, The Cochrane Library, Web of Science, and Embase. Data were pooled using the number of events/number of evaluable patients (non-small cell lung cancer patients with BMs) according to fixed or random effect models. Intracranial efficacy was assessed through overall response rate (ORR), disease control rate (DCR), and median progression-free survival (PFS). Subgroup analyses for baseline BMs, previous treatment with ALK inhibitor, study type, and current ALK inhibitor were made. Twenty studies accounting for 2,715 patients were included. The pooled iORR was 48% (95% CI: 32-63%) in fifteen single-arm studies. The overall DCR was 65% (95% CI: 60-69%) from three studies include available data. The iORR was 79% (95% CI: 64-91%), 45% (24-67%), 48% (34-63%), 18% (13-24%) in patients receiving alectinib, ceritinib, brigatinib, and crizotinib, respectively. Five randomized studies assessed the intracranial efficacy of anti-ALK agents versus chemotherapy, the pooled RR for iORR was 3.54 (95% CI: 2.38-5.26), and the pooled HR for iPFS was 0.52 (95% CI: 0.36-0.75; P=0.71) estimated in 2 studies. Despite the limitation from lack of published clinical data, our results showed that ALK inhibitors are effective at the brain site regardless of previous anti-ALK treatments, systemic therapy with ALK inhibitors should be considered as a preferred approach over for controlling BMs from ALK-positive NSCLC.