Efficacy and safety of ceritinib in anaplastic lymphoma kinase-rearranged non-small cell lung cancer: A systematic review and meta-analysis.

Abstract

What is known and objectiveCeritinib is a new, oral, potent and selective second‐generation anaplastic lymphoma kinase (ALK) inhibitor approved by the Food and Drug Administration of the United States in April 2014. It is active in crizotinib‐resistant patients, especially in patients with non‐small cell lung cancer (NSCLC) and brain metastasis. The aim of this study was to analyse the effects and side effects of ceritinib in ALK‐rearranged NSCLC.MethodsWe searched articles published from January 1980 to March 2019 in PubMed, EMBASE, Cochrane Library and Web of Science. The pooled estimate and 95% CI were calculated with DerSimonian‐Laird method and the random effect model.Results and discussionFrom 15 articles, 2,598 patients were included in the meta‐analysis. Eleven studies reported the ORR, and the DCR was presented in 10 studies. The ORR and DCR of ceritinib were 0.48 (95% CI, 0.39‐0.57) and 0.76 (95% CI, 0.69‐0.82), respectively. The PFS and OS were presented in nine and three eligible studies, respectively. The PFS and OS of ceritinib were 7.26 months (95% CI, 5.10‐9.43) and 18.73 months (95% CI; 14.59‐22.87). These results suggested that ceritinib can effectively treat patients with ALK‐rearranged NSCLC. Diarrhoea, nausea and vomiting were the three most common AEs and occurred in 69% (95% CI 51.7‐87.1%), 66% (95% CI 47.0‐85.8%) and 51% (95% CI 35.9‐66.8%) of patients, respectively. Considering serious gastrointestinal AEs, antiemetic and antidiarrhoeal drugs should be considered to improve a patient's tolerance to ceritinib.What is new and conclusionCeritinib is effective in the treatment of patients with ALK‐rearranged NSCLC with crizotinib resistance. The DCR was up to 76%, and PFS was extended to 7.6 months. The AEs were acceptable.