PMID- 35435628 OWN - NLM STAT- MEDLINE DCOM- 20220719 LR - 20220818 IS - 1573-0646 (Electronic) IS - 0167-6997 (Linking) VI - 40 IP - 4 DP - 2022 Aug TI - Toxicity profile of anaplastic lymphoma kinase tyrosine kinase inhibitors for patients with non-small cell lung cancer: A systematic review and meta-analysis. PG - 831-840 LID - 10.1007/s10637-022-01242-6 [doi] AB - Anaplastic lymphoma kinase (ALK) inhibitors are commonly used for patients harboring ALK-positive non-small cell lung cancer (NSCLC). This meta-analysis was conducted to evaluate the toxicity profile of ALK inhibitors. Pubmed, Web of Science, Embase, and the Cochrane Central Register of Controlled Trials databases were systematically searched for clinical trials conducted in advanced NSCLC treated with ALK inhibitors. The incidences of pooled adverse events (AEs) were conducted using the random effects model. We included 30 studies in the meta-analysis. Almost all patients receiving ALK inhibitor monotherapy occurred at least one AE. The pooled incidences of grade >/= 3 AEs were 71.3% for ceritinib 750 mg, 44.6% for crizotinib, 37.4% for alectinib, and 35.3% for ensartinib. Only one study each reported the incidence of grade >/= 3 AEs for brgatinib (72.8%), lorlatinib (72.4%), and ceritinib 450 mg (64.8%), respectively. The rates of dose reduction due to AEs ranking from high to low were ceritinib 750 mg, brigatinib, ceritinib 450 mg, lorlatinib, crizotinib, ensartinib, and alectinib. The rates of treatment discontinuation due to AEs were low, ranging from 3.8% to 10.5%. Gastrointestinal AEs were most common for ceritinib 750 mg. Hepatic transaminases elevation was mostly observed in ceritinib and brigatinib. Rash frequently occurred for ensartinib. Lorlatinib had a high incidence of hypertriglyceridemia and hypercholesterolemia, which were rarely reported in other ALK inhibitors. The incidences of grade >/= 3 AEs for individual ALK inhibitor were moderately high yet manageable. Different toxicity spectrums were found in each ALK inhibitor. CI - (c) 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. FAU - Tao, Yunxia AU - Tao Y AD - Department of Medical Oncology, Key Laboratory of Clinical Study On Anticancer Molecular Targeted Drugs, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 17 Panjiayuan Nanli, Chaoyang District, Beijing, 100021, China. FAU - Zhou, Yu AU - Zhou Y AD - Department of Medical Oncology, Key Laboratory of Clinical Study On Anticancer Molecular Targeted Drugs, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 17 Panjiayuan Nanli, Chaoyang District, Beijing, 100021, China. FAU - Tang, Le AU - Tang L AD - Department of Medical Oncology, Key Laboratory of Clinical Study On Anticancer Molecular Targeted Drugs, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 17 Panjiayuan Nanli, Chaoyang District, Beijing, 100021, China. FAU - Chen, Haizhu AU - Chen H AD - Department of Medical Oncology, Key Laboratory of Clinical Study On Anticancer Molecular Targeted Drugs, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 17 Panjiayuan Nanli, Chaoyang District, Beijing, 100021, China. FAU - Feng, Yu AU - Feng Y AD - Department of Medical Oncology, Key Laboratory of Clinical Study On Anticancer Molecular Targeted Drugs, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 17 Panjiayuan Nanli, Chaoyang District, Beijing, 100021, China. FAU - Shi, Yuankai AU - Shi Y AUID- ORCID: 0000-0002-8685-6744 AD - Department of Medical Oncology, Key Laboratory of Clinical Study On Anticancer Molecular Targeted Drugs, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 17 Panjiayuan Nanli, Chaoyang District, Beijing, 100021, China. syuankai@cicams.ac.cn. LA - eng PT - Journal Article PT - Meta-Analysis PT - Research Support, Non-U.S. Gov't PT - Review PT - Systematic Review DEP - 20220418 PL - United States TA - Invest New Drugs JT - Investigational new drugs JID - 8309330 RN - 0 (Lactams, Macrocyclic) RN - 0 (Protein Kinase Inhibitors) RN - 53AH36668S (Crizotinib) RN - EC 2.7.10.1 (Anaplastic Lymphoma Kinase) RN - EC 2.7.10.1 (Protein-Tyrosine Kinases) SB - IM MH - Anaplastic Lymphoma Kinase MH - *Carcinoma, Non-Small-Cell Lung/drug therapy MH - Crizotinib/adverse effects MH - Humans MH - Lactams, Macrocyclic MH - *Lung Neoplasms/drug therapy MH - Protein Kinase Inhibitors/adverse effects MH - Protein-Tyrosine Kinases OTO - NOTNLM OT - Adverse events OT - Anaplastic lymphoma kinase tyrosine kinase inhibitors OT - Meta-analysis OT - Non-small cell lung cancer EDAT- 2022/04/19 06:00 MHDA- 2022/07/20 06:00 CRDT- 2022/04/18 12:09 PHST- 2022/01/26 00:00 [received] PHST- 2022/03/29 00:00 [accepted] PHST- 2022/04/19 06:00 [pubmed] PHST- 2022/07/20 06:00 [medline] PHST- 2022/04/18 12:09 [entrez] AID - 10.1007/s10637-022-01242-6 [pii] AID - 10.1007/s10637-022-01242-6 [doi] PST - ppublish SO - Invest New Drugs. 2022 Aug;40(4):831-840. doi: 10.1007/s10637-022-01242-6. Epub 2022 Apr 18.