The efficacy and safety of crizotinib in the treatment of anaplastic lymphoma kinase-positive non-small cell lung cancer: a meta-analysis of clinical trials.

BACKGROUND: Crizotinib was granted accelerated approval by the Food and Drug Administration in 2011 for the treatment of anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC). To evaluate the efficacy and safety of crizotinib, we performed a meta-analysis of published clinical trials using the random effect model.

METHODS: The efficacy and safety of crizotinib was evaluated based on 1-year overall survival (OS), progression-free survival (PFS), overall response rate (ORR), partial response, complete response, stable disease, and dose reduction or cessation because of crizotinib toxicity.

RESULTS: Six clinical trials were included in the meta-analysis. Crizotinib treatment demonstrated a 1-year OS of 66.8% (95% CI, 52.2-78.8%) and a PFS of 8.6 months (95% CI, 7.3-9.9 months). The aggregate ORR, partial response and complete response rates were 61.2%, 59.8% and 1.5%, respectively. The proportion of patients achieving stable disease was 42.6% (95% CI, 17.3-72.5%). The most frequently reported adverse effects of crizotinib were mild visual disturbances, nausea, vomiting, diarrhea, constipation, edema, reduction in glomerular filtration rate, and generally reversible but sometimes severe elevations in aspartate aminotransferase and alanine aminotransferase. The proportion of patients who required dose reduction or cessation because of crizotinib toxicity was 6.5% (95% CI, 4.1-10.1%).

CONCLUSIONS: This meta-analysis revealed extended survival and improved response rates in patients treated with crizotinib. As a novel, targeted anticancer agent, crizotinib appears to be a favorable treatment option for patients with locally advanced or metastatic ALK-positive NSCLC.