PMID- 28606126 OWN - NLM STAT- MEDLINE DCOM- 20180326 LR - 20240326 IS - 1471-2407 (Electronic) IS - 1471-2407 (Linking) VI - 17 IP - 1 DP - 2017 Jun 12 TI - Pooled safety analyses of ALK-TKI inhibitor in ALK-positive NSCLC. PG - 412 LID - 10.1186/s12885-017-3405-3 [doi] LID - 412 AB - BACKGROUND: The anaplastic lymphoma kinase tyrosine kinase inhibitors (ALK-TKIs) have been administered to patients with ALK-positive non-small cell lung cancer for a long period of time and show a promising response. However, the differences in the toxicity profiles among these drugs are still unclear. METHODS: We performed a comprehensive search of the MEDLINE, EMBASE, WEB OF SCIENCE and COCHRANE databases from the drugs' inception to May 2016 to identify clinical trials. Severe adverse events (AEs) (grade >/= 3) based on the ALK-TKI type were analysed. RESULTS: Seventeen trials published between 2011 and 2016, including a total of 1826 patients, were eligible for analysis. Patients in 10 trials (n = 1000) received crizotinib, patients in 5 trials (n = 601) received ceritinib and patients in 2 trials (n = 225) received alectinib. The overall frequencies of treatment-related death and AEs due to treatment withdrawal were 0.9% (12/1365) and 5.5% (85/1543), respectively. Moreover, the frequency of severe AEs in patients treated with ceritinib was significantly higher than patients treated with crizotinib or alectinib, especially for hepatotoxicity, fatigue and some of gastrointestinal symptoms. Additionally, significant difference in the elevated lipase and amylase levels (grade >/= 3) were detected between ceritinib and crizotinib/alectinib, whereas neutropenia was less frequent. CONCLUSIONS: ALK-TKIs were safe for ALK-positive patients. Moreover, statistically significant differences in some severe AEs among ceritinib, crizotinib and alectinib were detected in present study. FAU - Zhu, Qian AU - Zhu Q AD - State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, People's Republic of China. AD - Department of Biotherapy, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People's Republic of China. FAU - Hu, Hao AU - Hu H AD - Department of Thoracic Surgery, Medical College of Nanchang University, Nanchang, 330006, People's Republic of China. FAU - Weng, De-Sheng AU - Weng DS AD - State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, People's Republic of China. AD - Department of Biotherapy, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People's Republic of China. FAU - Zhang, Xiao-Fei AU - Zhang XF AD - State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, People's Republic of China. AD - Department of Biotherapy, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People's Republic of China. FAU - Chen, Chang-Long AU - Chen CL AD - State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, People's Republic of China. AD - Department of Biotherapy, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People's Republic of China. FAU - Zhou, Zi-Qi AU - Zhou ZQ AD - State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, People's Republic of China. AD - Department of Biotherapy, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People's Republic of China. FAU - Tang, Yan AU - Tang Y AD - State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, People's Republic of China. AD - Department of Biotherapy, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People's Republic of China. FAU - Xia, Jian-Chuan AU - Xia JC AD - State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, People's Republic of China. xiajch@mail.sysu.edu.cn. AD - Department of Biotherapy, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People's Republic of China. xiajch@mail.sysu.edu.cn. LA - eng PT - Journal Article PT - Meta-Analysis DEP - 20170612 PL - England TA - BMC Cancer JT - BMC cancer JID - 100967800 RN - 0 (Carbazoles) RN - 0 (Piperidines) RN - 0 (Protein Kinase Inhibitors) RN - 0 (Pyrazoles) RN - 0 (Pyridines) RN - 0 (Pyrimidines) RN - 0 (Sulfones) RN - 53AH36668S (Crizotinib) RN - EC 2.7.10.1 (ALK protein, human) RN - EC 2.7.10.1 (Anaplastic Lymphoma Kinase) RN - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases) RN - K418KG2GET (ceritinib) RN - LIJ4CT1Z3Y (alectinib) SB - IM MH - Anaplastic Lymphoma Kinase MH - Carbazoles/adverse effects/therapeutic use MH - Carcinoma, Non-Small-Cell Lung/*drug therapy/enzymology MH - Clinical Trials as Topic MH - Crizotinib MH - Female MH - Humans MH - Lung Neoplasms/*drug therapy/enzymology MH - Male MH - *Patient Safety MH - Piperidines/adverse effects/therapeutic use MH - Protein Kinase Inhibitors/*adverse effects/therapeutic use MH - Pyrazoles/adverse effects/therapeutic use MH - Pyridines/adverse effects/therapeutic use MH - Pyrimidines/adverse effects/therapeutic use MH - Receptor Protein-Tyrosine Kinases/*antagonists & inhibitors MH - Sulfones/adverse effects/therapeutic use PMC - PMC5469041 OTO - NOTNLM OT - Alectinib OT - Anaplastic lymphoma kinase OT - Ceritinib OT - Crizotinib OT - Non-small-cell lung cancer OT - Tyrosine kinase inhibitors EDAT- 2017/06/14 06:00 MHDA- 2018/03/27 06:00 PMCR- 2017/06/12 CRDT- 2017/06/14 06:00 PHST- 2016/08/14 00:00 [received] PHST- 2017/06/07 00:00 [accepted] PHST- 2017/06/14 06:00 [entrez] PHST- 2017/06/14 06:00 [pubmed] PHST- 2018/03/27 06:00 [medline] PHST- 2017/06/12 00:00 [pmc-release] AID - 10.1186/s12885-017-3405-3 [pii] AID - 3405 [pii] AID - 10.1186/s12885-017-3405-3 [doi] PST - epublish SO - BMC Cancer. 2017 Jun 12;17(1):412. doi: 10.1186/s12885-017-3405-3.