Effect of ALK-inhibitors in the treatment of non-small cell lung cancer: a systematic review and meta-analysis.

OBJECTIVE Lung cancer is the leading cause of cancer-related mortality. Over 80% of all lung cancer cases are non-small-cell lung cancer (NSCLC) and approximately 5% of NSCLC patients are positive for anaplastic lymphoma kinase (ALK) gene rearrangement or fusion with echinoderm microtubule-associated protein-like 4 (EML4). NSCLC patients with positive ALK-EML4 gene fusion are highly sensitive to ALK-inhibitors. While the efficacy of the ALK-inhibitors in the treatment of NSCLC has been consistently reported, a limited number of randomized, large-scale clinical trials have been reported. The current study was, therefore, designed to systematically review and appraise current knowledge and conduct a meta-analysis on phase I, II, and III clinical trials in which ALK-inhibitors were used to treat NSCLC. MATERIALS AND METHODS The PubMed online database was thoroughly searched. A total of 26 articles were included in a qualitative systematic review, and four of them were used to conduct the quantitative meta-analysis. RESULTS We found that ALK inhibitors significantly improved the overall survival (OS) and progress free survival (PFS) of NSCLC patients, especially of ALK or ROS1 gene fusion-positive cases. ALK inhibitors contributed to better therapeutic outcomes regarding increased one-year and two-year OS, PFS, and ORR (Odds ratio: 4.393, 95% CI: 3.302-5.845, p < 0.001). Visual disturbance was the most common side effect observed in the patients treated with crizotinib, whereas mild gastrointestinal reactions, such as diarrhea and nausea, were most frequent in the patients treated with the 2nd generation of ALK inhibitors. CONCLUSIONS ALK inhibitors are safe and effective in the treatment of NSCLC patients, especially those with positive ALK-EML4 gene fusion or rearrangement.