{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T12:40:28Z","timestamp":1789389628322,"version":"build-2803163510"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,8,20]],"date-time":"2024-08-20T00:00:00Z","timestamp":1724112000000},"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>Antibody-drug conjugates (ADCs) have emerged as the focus and hotspots in the cancer field, yet the accompanying ocular toxicity has often been underestimated. We aimed to comprehensively and comparatively analyze the risk of ocular toxicity associated with various ADCs using the FDA Adverse Event Reporting System (FAERS) database.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Data were extracted from the FAERS database from Q3 2011 to Q3 2023. We analyzed the clinical characteristics of ADCs-related ocular adverse events (AEs). These data were further mined by proportional analysis and Bayesian approach to detect signals of ADCs-induced ocular AEs. Moreover, the time to onset of ocular toxicity was also evaluated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 1,246 cases of ocular AEs were attributed to ADCs. Ocular toxicity signals were observed in patients treated with belantamab mafodotin, brentuximab vedotin, enfortumab vedotin, mirvetuximab soravtansine, sacituzumab govitecan, trastuzumab deruxtecan, and trastuzumab emtansine. Of these, belantamab mafodotin, trastuzumab emtansine, and mirvetuximab soravtansine, whose payloads are microtubule polymerization inhibitors, were more susceptible to ocular toxicity. The ten most common ADCs-related ocular AEs signals are keratopathy [ROR = 1,273.52, 95% CI (1,129.26\u20131,436.21)], visual acuity reduced [ROR = 22.83, 95% CI (21.2\u201324.58)], dry eye [ROR = 9.69, 95% CI (8.81\u201310.66)], night blindness [ROR = 259.87, 95% CI (228.23\u2013295.89)], vision blurred [ROR = 1.78, 95% CI (1.57\u20132.02)], photophobia [ROR = 10.45, 95% CI (9.07\u201312.05)], foreign body sensation in eyes [ROR = 23.35, 95% CI (19.88\u201327.42)], ocular toxicity [ROR = 144.62, 95% CI (117.3\u2013178.32)], punctate keratitis [ROR = 126.21, 95% CI (101.66\u2013156.69)], eye disorder [ROR = 2.71, 95% CI (2.21\u20133.32)]. In terms of onset time, sacituzumab govitecan displayed an earlier onset of 21\u00a0days, while trastuzumab deruxtecan exhibited the latest onset of 223\u00a0days.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>ADCs may increase the risk of ocular toxicity in cancer patients, leading to serious mortality. With the widespread application of newly launched ADCs, combining the FAERS data with other data sources is crucial for monitoring the ocular toxicity of ADCs. In addition, novel ocular toxicity signals not documented in product labeling were detected. Further research will be necessary to validate our findings in the future.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2024.1425617","type":"journal-article","created":{"date-parts":[[2024,8,20]],"date-time":"2024-08-20T01:00:03Z","timestamp":1724115603000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":37,"title":["Ocular adverse events associated with antibody-drug conjugates in oncology: a pharmacovigilance study based on FDA adverse event reporting system (FAERS)"],"prefix":"10.3389","volume":"15","author":[{"given":"KaiLi","family":"Mao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"HuaYu","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"SongYang","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"HongLiang","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"LuYao","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,8,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"410","DOI":"10.1016\/j.urolonc.2021.10.002","article-title":"The management of toxicities from immune, targeted and ADCs treatments in patients with urothelial cancer","volume":"41","author":"Atiq","year":"2023","journal-title":"Urologic Oncol. Seminars Orig. Investigations"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1124","DOI":"10.1016\/S1470-2045(19)30328-6","article-title":"Trastuzumab duocarmazine in locally advanced and metastatic solid tumours and HER2-expressing breast cancer: a phase 1 dose-escalation and dose-expansion study","volume":"20","author":"Banerji","year":"2019","journal-title":"Lancet Oncol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"792","DOI":"10.1097\/ICO.0000000000002934","article-title":"Refractive shifts and changes in corneal curvature associated with antibody\u2013drug conjugates","volume":"41","author":"Canestraro","year":"2022","journal-title":"Cornea"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1616","DOI":"10.1002\/ijc.34848","article-title":"Ocular toxicity associated with anti\u2010HER2 agents in breast cancer: a pharmacovigilance analysis using the FAERS database","volume":"154","author":"Chen","year":"2024","journal-title":"Intl J. Cancer"},{"key":"B5","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1016\/S1470-2045(21)00056-5","article-title":"Efficacy and safety of tisotumab vedotin in previously treated recurrent or metastatic cervical cancer (innovaTV 204\/GOG-3023\/ENGOT-cx6): a multicentre, open-label, single-arm, phase 2 study","volume":"22","author":"Coleman","year":"2021","journal-title":"Lancet Oncol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1186\/s13045-021-01035-z","article-title":"Antibody\u2013drug conjugates in solid tumors: a look into novel targets","volume":"14","author":"Criscitiello","year":"2021","journal-title":"J. Hematol. Oncol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1089\/jop.2015.0064","article-title":"Ocular adverse events associated with antibody\u2013drug conjugates in human clinical trials","volume":"31","author":"Eaton","year":"2015","journal-title":"J. Ocular Pharmacol. Ther."},{"key":"B8","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1097\/PPO.0000000000000627","article-title":"Strategies for mitigating antibody-drug conjugate related adverse events for precision therapy","volume":"28","author":"Gouda","year":"2022","journal-title":"Cancer J."},{"key":"B9","doi-asserted-by":"publisher","first-page":"4764","DOI":"10.3390\/molecules25204764","article-title":"Antibody\u2013drug conjugates for cancer therapy","volume":"25","author":"Hafeez","year":"2020","journal-title":"Molecules"},{"key":"B10","doi-asserted-by":"publisher","first-page":"1100","DOI":"10.1111\/iju.14925","article-title":"Current status and future prospects of antibody\u2013drug conjugates in urological malignancies","volume":"29","author":"Hayashi","year":"2022","journal-title":"Int J Urology"},{"key":"B11","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1089\/jop.2023.0069","article-title":"Antibody-drug conjugates and ocular toxicity","volume":"39","author":"Jaffry","year":"2023","journal-title":"J. Ocular Pharmacol. Ther."},{"key":"B12","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1038\/s41409-017-0019-y","article-title":"Management of important adverse events associated with inotuzumab ozogamicin: expert panel review","volume":"53","author":"Kebriaei","year":"2018","journal-title":"Bone Marrow Transpl."},{"key":"B13","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1158\/1541-7786.MCR-19-0582","article-title":"Antibody\u2013drug conjugates: a comprehensive review","volume":"18","author":"Khongorzul","year":"2020","journal-title":"Mol. Cancer Res."},{"key":"B14","doi-asserted-by":"publisher","first-page":"442","DOI":"10.3390\/ph14050442","article-title":"The chemistry behind ADCs","volume":"14","author":"Kostova","year":"2021","journal-title":"Pharmaceuticals"},{"key":"B15","doi-asserted-by":"publisher","first-page":"1015","DOI":"10.1007\/s12325-017-0519-6","article-title":"Antibody\u2013drug conjugates (ADCs) for personalized treatment of solid tumors: a review","volume":"34","author":"Lambert","year":"2017","journal-title":"Adv. Ther."},{"key":"B16","doi-asserted-by":"publisher","first-page":"561","DOI":"10.3390\/ijms17040561","article-title":"Linkers having a crucial role in antibody\u2013drug conjugates","volume":"17","author":"Lu","year":"2016","journal-title":"IJMS"},{"key":"B17","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1007\/s12272-023-01447-0","article-title":"Antibody drug conjugates as targeted cancer therapy: past development, present challenges and future opportunities","volume":"46","author":"Maiti","year":"2023","journal-title":"Arch. Pharm. Res."},{"key":"B18","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1007\/s10637-017-0520-6","article-title":"Clinical toxicity of antibody drug conjugates: a meta-analysis of payloads","volume":"36","author":"Masters","year":"2018","journal-title":"Invest. New Drugs"},{"key":"B19","doi-asserted-by":"publisher","first-page":"101133","DOI":"10.1016\/j.ajoc.2021.101133","article-title":"Structural changes of corneal epithelium in belantamab-associated superficial keratopathy using anterior segment optical coherence tomography","volume":"23","author":"Matsumiya","year":"2021","journal-title":"Am. J. Ophthalmol. Case Rep."},{"key":"B20","doi-asserted-by":"publisher","first-page":"1727","DOI":"10.1158\/1078-0432.CCR-18-2474","article-title":"Evaluation of prophylactic corticosteroid eye drop use in the management of corneal abnormalities induced by the antibody\u2013drug conjugate mirvetuximab soravtansine","volume":"25","author":"Matulonis","year":"2019","journal-title":"Clin. Cancer Res."},{"key":"B21","doi-asserted-by":"publisher","first-page":"746","DOI":"10.1177\/0192623318803059","article-title":"A brief introduction to antibody\u2013drug conjugates for toxicologic pathologists","volume":"46","author":"Mecklenburg","year":"2018","journal-title":"Toxicol. Pathol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1097\/ICO.0000000000003162","article-title":"Dupilumab-induced, tralokinumab-induced, and belantamab mafodotin\u2013induced adverse ocular events\u2014incidence, etiology, and management","volume":"42","author":"Mickevicius","year":"2023","journal-title":"Cornea"},{"key":"B24","doi-asserted-by":"publisher","first-page":"921","DOI":"10.1080\/14740338.2023.2251380","article-title":"Ocular toxicities associated with antibody drug conjugates and immunotherapy in oncology: clinical presentation, pathogenesis, and management strategies","volume":"22","author":"Raheem","year":"2023","journal-title":"Expert Opin. Drug Saf."},{"key":"B25","doi-asserted-by":"publisher","first-page":"3277","DOI":"10.1200\/JCO.2011.41.5851","article-title":"Ocular toxicity of targeted therapies","volume":"30","author":"Renouf","year":"2012","journal-title":"JCO"},{"key":"B26","doi-asserted-by":"publisher","first-page":"796","DOI":"10.7150\/ijms.6048","article-title":"Data mining of the public version of the FDA adverse event reporting system","volume":"10","author":"Sakaeda","year":"2013","journal-title":"Int. J. Med. Sci."},{"key":"B27","doi-asserted-by":"publisher","first-page":"108","DOI":"10.2174\/1574892817666220729121205","article-title":"Antibody-drug conjugates for breast cancer treatment","volume":"18","author":"Sheikh","year":"2023","journal-title":"PRA"},{"key":"B28","doi-asserted-by":"publisher","first-page":"563","DOI":"10.1080\/14740338.2022.2016696","article-title":"A real-world pharmacovigilance study of axitinib: data mining of the public version of FDA adverse event reporting system","volume":"21","author":"Shu","year":"","journal-title":"Expert Opin. Drug Saf."},{"key":"B29","doi-asserted-by":"publisher","first-page":"996179","DOI":"10.3389\/fpubh.2022.996179","article-title":"Gastrointestinal adverse events associated with semaglutide: a pharmacovigilance study based on FDA adverse event reporting system","volume":"10","author":"Shu","year":"","journal-title":"Front. Public Health"},{"key":"B30","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1159\/000505376","article-title":"Fractures due to aromatase inhibitor therapy for breast cancer: a real-world analysis of FAERS data in the past 15 years","volume":"43","author":"Song","year":"2020","journal-title":"Oncol. Res. Treat."},{"key":"B31","doi-asserted-by":"publisher","first-page":"2067","DOI":"10.3324\/haematol.2022.281455","article-title":"Hemophagocytic lymphohistiocytosis and disseminated intravascular coagulation are underestimated, but fatal adverse events in chimeric antigen receptor T-cell therapy","volume":"108","author":"Song","year":"2023","journal-title":"haematol"},{"key":"B32","doi-asserted-by":"publisher","first-page":"476","DOI":"10.1097\/CCO.0000000000000108","article-title":"Antibody drug conjugates","volume":"26","author":"Teicher","year":"2014","journal-title":"Curr. Opin. Oncol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"2168","DOI":"10.1093\/annonc\/mdw424","article-title":"Antibody drug conjugates: lessons from 20 years of clinical experience","volume":"27","author":"Tolcher","year":"2016","journal-title":"Ann. Oncol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1038\/s41571-023-00850-2","article-title":"Exploring the next generation of antibody\u2013drug conjugates","volume":"21","author":"Tsuchikama","year":"2024","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"1378","DOI":"10.1097\/ICO.0000000000000868","article-title":"Abnormal corneal lesions induced by trastuzumab emtansine: an antibody\u2013drug conjugate for breast cancer","volume":"35","author":"Tsuda","year":"2016","journal-title":"Case Rep."},{"key":"B36","doi-asserted-by":"publisher","first-page":"678634","DOI":"10.3389\/fonc.2021.678634","article-title":"Ocular toxicity of belantamab mafodotin, an oncological perspective of management in relapsed and refractory multiple myeloma","volume":"11","author":"Wahab","year":"2021","journal-title":"Front. Oncol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1002\/cncr.34507","article-title":"Treatment-related adverse events of antibody\u2013drug conjugates in clinical trials: a systematic review and meta-analysis","volume":"129","author":"Zhu","year":"2023","journal-title":"Cancer"}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2024.1425617\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,20]],"date-time":"2024-08-20T01:00:06Z","timestamp":1724115606000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2024.1425617\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,20]]},"references-count":36,"alternative-id":["10.3389\/fphar.2024.1425617"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2024.1425617","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,20]]},"article-number":"1425617"}}