PMID- 33382906 OWN - NLM STAT- MEDLINE DCOM- 20220103 LR - 20230920 IS - 1752-8062 (Electronic) IS - 1752-8054 (Print) IS - 1752-8054 (Linking) VI - 14 IP - 3 DP - 2021 May TI - Adverse event profiles of epidermal growth factor receptor-tyrosine kinase inhibitors in cancer patients: A systematic review and meta-analysis. PG - 919-933 LID - 10.1111/cts.12957 [doi] AB - The efficacy of agents targeting epidermal growth factor receptor (EGFR) in patients with various cancers was well elucidated. However, the safety profile of EGFR tyrosine kinase inhibitors (EGFR-TKIs) has not been systematically investigated. This meta-analysis aimed to evaluate the safety profile of EGFR-TKIs in patients with cancer. A systematic search of PubMed, EMBASE, Cochrane Library databases, ASCO, and ESMO abstracts were conducted. Randomized controlled trials (RCTs) that compared safety profile of EGFR-TKIs with placebo were included. The end points included treatment-related adverse events (AEs), treatment discontinuation, and toxic death. Twenty-eight RCTs containing 17,800 patients were included. The analyses showed that the most frequently observed all-grade AEs in patients treated with EGFR-TKIs were diarrhea (53.7%), rash (48.6%), mucositis (46.5%), alanine aminotransferase (ALT) increased (38.9%), and skin reaction (35.2%). The most common high-grade (grade >/=3) AEs were mucositis (14.8%), pain (8.2%,), metabolism and nutrition disorders (7.4%), diarrhea (6.2%), dyspnea (6.1%), and hypertension (6.1%). The incidence of serious AEs, treatment discontinuation, and toxic death due to AEs were 18.2%, 12.36%, and 3.0%, respectively. Pooled risk ratio (RR) showed that the use of EGFR-TKIs was associated with an increased risk of developing AEs. Subgroup analysis indicated that the risk of AEs varied significantly according to tumor type, generation line, and drug type. Our meta-analysis indicates EGFR-TKIs was associated with a significant increased risk of a series of unique AEs. Early detection and proper management of AEs are important to reduce morbidity, avoid treatment discontinuation, and improve patient quality of life. Study Highlights WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC? The safety profile of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) varied in different trials, and has not been systemically investigated. WHAT QUESTION DID THIS STUDY ADDRESS? We conducted this meta-analysis of randomized control trials (RCTs) to provide a comprehensive evaluation of adverse event in patients with cancer receiving EGFR-TKIs. WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE? Our meta-analysis indicates EGFR-TKIs was associated with a significant increased risk of a series of unique adverse events (AEs). HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE? The integrated understanding of safety profile of EGFR-TKIs will help in the future design of new EGFR-TKIs with a better safety profile. CI - (c) 2020 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of the American Society for Clinical Pharmacology and Therapeutics. FAU - Yin, Xiaonan AU - Yin X AD - Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China. FAU - Zhao, Zhou AU - Zhao Z AD - Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China. FAU - Yin, Yuan AU - Yin Y AD - Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China. FAU - Shen, Chaoyong AU - Shen C AD - Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China. FAU - Chen, Xin AU - Chen X AD - Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China. FAU - Cai, Zhaolun AU - Cai Z AD - Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China. FAU - Wang, Jian AU - Wang J AD - Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China. FAU - Chen, Zhixin AU - Chen Z AD - Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China. FAU - Yin, Yiqiong AU - Yin Y AD - Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China. FAU - Zhang, Bo AU - Zhang B AD - Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China. LA - eng PT - Journal Article PT - Meta-Analysis PT - Research Support, Non-U.S. Gov't PT - Systematic Review DEP - 20210125 PL - United States TA - Clin Transl Sci JT - Clinical and translational science JID - 101474067 RN - 0 (Protein Kinase Inhibitors) RN - EC 2.7.10.1 (EGFR protein, human) RN - EC 2.7.10.1 (ErbB Receptors) SB - IM MH - Drug-Related Side Effects and Adverse Reactions/diagnosis/*epidemiology/etiology MH - ErbB Receptors/antagonists & inhibitors/genetics MH - Humans MH - Incidence MH - Neoplasms/*drug therapy/genetics MH - Protein Kinase Inhibitors/*adverse effects MH - Randomized Controlled Trials as Topic MH - Severity of Illness Index PMC - PMC8212741 COIS- The other authors declared no competing interests for this work. EDAT- 2021/01/01 06:00 MHDA- 2022/01/04 06:00 PMCR- 2021/05/01 CRDT- 2020/12/31 17:10 PHST- 2020/11/06 00:00 [revised] PHST- 2020/08/11 00:00 [received] PHST- 2020/11/08 00:00 [accepted] PHST- 2021/01/01 06:00 [pubmed] PHST- 2022/01/04 06:00 [medline] PHST- 2020/12/31 17:10 [entrez] PHST- 2021/05/01 00:00 [pmc-release] AID - CTS12957 [pii] AID - 10.1111/cts.12957 [doi] PST - ppublish SO - Clin Transl Sci. 2021 May;14(3):919-933. doi: 10.1111/cts.12957. Epub 2021 Jan 25.