{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T01:59:17Z","timestamp":1792720757461,"version":"4.5.0"},"reference-count":69,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T00:00:00Z","timestamp":1741651200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors (EGFR-TKIs) in clinical use show promise but can cause AEs, impacting patients\u2019 wellbeing and increasing costs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This study utilized two methods: network meta-analysis (NMA) and disproportionality analysis (DA). For NMA, we searched PubMed, Embase, Cochrane Central Register of Controlled Trials, and\n                      <jats:ext-link>ClinicalTrials.gov<\/jats:ext-link>\n                      up to 10 September 2024, for phase II\/III RCTs comparing EGFR-TKI monotherapy with chemotherapy or other EGFR-TKIs. Using STATA 18.0, we calculated odds ratios (ORs) with 95% confidence intervals (CIs) and assessed heterogeneity via Chi-squared and I\n                      <jats:sup>2<\/jats:sup>\n                      tests. Adverse events (AEs) were ranked using the surface under the cumulative ranking curve (SUCRA). For DA, we analyzed FAERS data (January 2004-June 2024), evaluating AE signals with reporting odds ratios (RORs) and 95% CIs; signals were considered significant if the ROR and its 95% CI lower bound exceeded 1. Primary outcomes for NMA included all-grade AEs, grade \u22653 AEs, specific AEs, and AE-related mortality. For DA, outcomes included EGFR-TKI as the primary AE cause, time from treatment to AE, and AE-related mortality.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>NMA: 48% of EGFR-TKI patients experienced AEs, with 32.7% being severe. Afatinib showed highest toxicity; Icotinib was safest. Osimertinib was associated with highest risks of leukopenia (8%) and thrombocytopenia (9%). DA: Osimertinib had strongest links to cardiac diseases and blood\/lymphatic disorders. Gefitinib had the strongest signal for interstitial lung diseases; Erlotinib for anorexia. Most AEs occurred within 30\u00a0days, but cardiac disorders had a median onset of 41\u00a0days. Osimertinib had the highest AE-related mortality, with cardiac disorders leading in fatalities.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study used NMA and DA to explore EGFR-TKI-related AEs. Drugs varied in AE profiles, mostly mild, but Osimertinib and Dacomitinib were associated with more severe events. Osimertinib carried a high cardiac risk, delayed onset, and high mortality. Thus, comprehensive patient assessment and close monitoring are crucial with EGFR-TKI use.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2025.1519849","type":"journal-article","created":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T03:07:10Z","timestamp":1741662430000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["Adverse event profiles of EGFR-TKI: network meta-analysis and disproportionality analysis of the FAERS database"],"prefix":"10.3389","volume":"16","author":[{"given":"Jing","family":"Shi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinya","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengjiao","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Chai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiawei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanming","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,3,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1440","DOI":"10.1183\/13993003.02358-2014","article-title":"Erlotinib versus carboplatin and paclitaxel in advanced lepidic adenocarcinoma: IFCT-0504","volume":"46","author":"Cadranel","year":"2015","journal-title":"Eur. 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