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

Background: 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. Methods: 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. Results: 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. Conclusions: 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.