Efficacy and safety of anaplastic lymphoma kinase inhibitors for non-small cell lung cancer: A systematic review and network meta-analysis.

Background: To assess the efficacy and safety of anaplastic lymphoma kinase inhibitors (ALKIs) for the treatment of advanced-stage ALK rearrangement-positive non-small cell lung cancer (NSCLC).

Methods: We searched PubMed, EMBASE, and the Cochrane Library for randomized controlled trials (RCTs) that included patients with ALK-positive NSCLC receiving ALKIs. The outcomes of the study included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and treatment-related adverse events (TRAEs) of grade ≥3.

Results: A total of 12 RCTs consisting of 3169 patients with eight treatment options were included in this study. Our results showed that ALKIs have superior efficacy in OS, PFS, and ORR than chemotherapy or crizotinib (first-generation ALKI). Our study showed that only alectinib has a significant improvement in OS compared to chemotherapy (hazard ratio [HR], 0.61; 95% confidence interval [CI], 0.40-0.94). Alectinib appeared to have better OS than crizotinib (HR, 0.66; 95% CI, 0.45-0.95). Ensartinib has a significant PFS advantage over alectinib (HR, 0.62; 95% CI, 0.40-0.96). The surface under the ranking curve indicated that ensartinib (99.0%) was the highest rank regarding PFS. Moreover, both ensartinib and ceritinib showed significantly higher TRAEs of grade ≥3 compared with chemotherapy (risk ratios [RR], 2.74; 95% CI, 1.45-5.18; RR, 1.80; 95% CI, 1.26-2.57, respectively).

Conclusions: These results indicated that alectinib could be associated with the best therapeutic efficacy and well-tolerance AEs in the treatment of ALK-positive NSCLC.