PMID- 30771874 OWN - NLM STAT- MEDLINE DCOM- 20190410 LR - 20190410 IS - 1879-0461 (Electronic) IS - 1040-8428 (Linking) VI - 134 DP - 2019 Feb TI - Safety issues with the ALK inhibitors in the treatment of NSCLC: A systematic review. PG - 56-64 LID - S1040-8428(17)30250-0 [pii] LID - 10.1016/j.critrevonc.2018.11.004 [doi] AB - INTRODUCTION: Oral tyrosine kinase inhibitors targeting the chromosomal rearrangements of the anaplastic lymphoma kinase gene (ALK) in non-small cell lung cancer (NSCLC) were associated with superior clinical outcome. Tyrosine Kinase inhibitors (TKIs) are known to have peculiar toxicity profile, hence, increasing awareness to the safety profile of ALK inhibitors is essential. METHODS: A comprehensive systematic review of literature has been conducted to include prospective trials that used the ALK inhibitors Crizotinib, Ceritinib, Alectinib, Brigatinib and Lorlatinib in patients with advanced NSCLC and have available efficacy and toxicity results. RESULTS: A total of 14 studies including 2793 patients were considered eligible for our review and included two phase IB, seven phase II and five phase III studies. The most common adverse events (AEs) observed with ALK inhibitors were gastrointestinal (GI) toxicities as nausea (up to 83%), vomiting (up to 67%) and diarrhea (up to 86%), elevation of liver enzymes occurred in up to 60% and fatigue (up to 43%). There were differences in the toxicity patterns between the different ALK inhibitors with more GI and hepatic toxicities with Ceritinib, more visual disorders with Crizotinib, more dysgeusia with crizotinib and Alectinib and possibly more respiratory complications with Brigatinib. Most of the AEs were low grade and treatment-related deaths were associated with ALK inhibitors in 0-1% of patients. CONCLUSION: Most of adverse effects of ALKi can be managed efficiently via dose modifications or interruptions. Timely identification of each ALKi pattern of toxicity can prevent treatment-related morbidity and mortality in this palliative setting. CI - Copyright (c) 2018 Elsevier B.V. All rights reserved. FAU - Kassem, Loay AU - Kassem L AD - Clinical Oncology Department, Kasr Alainy School of Medicine, Cairo University, Cairo, Egypt. Electronic address: loay.kassem@cairocure.com. FAU - Shohdy, Kyrillus S AU - Shohdy KS AD - Clinical Oncology Department, Kasr Alainy School of Medicine, Cairo University, Cairo, Egypt. Electronic address: kerosam501@gmail.com. FAU - Lasheen, Shaimaa AU - Lasheen S AD - Clinical Oncology Department, Kasr Alainy School of Medicine, Cairo University, Cairo, Egypt. Electronic address: shaimaa_lash@hotmail.com. FAU - Abdel-Rahman, Omar AU - Abdel-Rahman O AD - Clinical Oncology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt. Electronic address: omar.abdelrhman@med.asu.edu.eg. FAU - Ali, Ahmad AU - Ali A AD - Clinical Oncology Department, Kasr Alainy School of Medicine, Cairo University, Cairo, Egypt. FAU - Abdel-Malek, Raafat R AU - Abdel-Malek RR AD - Clinical Oncology Department, Kasr Alainy School of Medicine, Cairo University, Cairo, Egypt. LA - eng PT - Journal Article PT - Systematic Review DEP - 20181201 PL - Netherlands TA - Crit Rev Oncol Hematol JT - Critical reviews in oncology/hematology JID - 8916049 RN - 0 (Protein Kinase Inhibitors) RN - EC 2.7.10.1 (ALK protein, human) RN - EC 2.7.10.1 (Anaplastic Lymphoma Kinase) SB - IM MH - Anaplastic Lymphoma Kinase/*antagonists & inhibitors MH - Carcinoma, Non-Small-Cell Lung/*drug therapy MH - Humans MH - Lung Neoplasms/*drug therapy MH - Protein Kinase Inhibitors/*standards/*therapeutic use MH - Safety OTO - NOTNLM OT - ALK inhibitors OT - Adverse effects OT - Non-small cell lung cancer EDAT- 2019/02/18 06:00 MHDA- 2019/04/11 06:00 CRDT- 2019/02/18 06:00 PHST- 2017/05/12 00:00 [received] PHST- 2018/02/04 00:00 [revised] PHST- 2018/11/20 00:00 [accepted] PHST- 2019/02/18 06:00 [entrez] PHST- 2019/02/18 06:00 [pubmed] PHST- 2019/04/11 06:00 [medline] AID - S1040-8428(17)30250-0 [pii] AID - 10.1016/j.critrevonc.2018.11.004 [doi] PST - ppublish SO - Crit Rev Oncol Hematol. 2019 Feb;134:56-64. doi: 10.1016/j.critrevonc.2018.11.004. Epub 2018 Dec 1.