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Ocular adverse events associated with antibody-drug conjugates in oncology: a pharmacovigilance study based on FDA adverse event reporting system (FAERS).

作者信息

Mao KaiLi, Chen Ping, Sun HuaYu, Zhong SongYang, Zheng HongLiang, Xu LuYao

机构信息

Department of Pharmacy, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Quzhou, Zhejiang, China.

出版信息

Front Pharmacol. 2024 Aug 20;15:1425617. doi: 10.3389/fphar.2024.1425617. eCollection 2024.


DOI:10.3389/fphar.2024.1425617
PMID:39228525
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11368736/
Abstract

BACKGROUND: 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. METHODS: 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. RESULTS: 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 (1,129.26-1,436.21)], visual acuity reduced [ROR = 22.83, 95% CI (21.2-24.58)], dry eye [ROR = 9.69, 95% CI (8.81-10.66)], night blindness [ROR = 259.87, 95% CI (228.23-295.89)], vision blurred [ROR = 1.78, 95% CI (1.57-2.02)], photophobia [ROR = 10.45, 95% CI (9.07-12.05)], foreign body sensation in eyes [ROR = 23.35, 95% CI (19.88-27.42)], ocular toxicity [ROR = 144.62, 95% CI (117.3-178.32)], punctate keratitis [ROR = 126.21, 95% CI (101.66-156.69)], eye disorder [ROR = 2.71, 95% CI (2.21-3.32)]. In terms of onset time, sacituzumab govitecan displayed an earlier onset of 21 days, while trastuzumab deruxtecan exhibited the latest onset of 223 days. CONCLUSION: 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.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d918/11368736/5a632c7f5402/fphar-15-1425617-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d918/11368736/c0d4785a2d9d/fphar-15-1425617-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d918/11368736/176bd22d6d3b/fphar-15-1425617-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d918/11368736/830090ba8105/fphar-15-1425617-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d918/11368736/5999911a6e47/fphar-15-1425617-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d918/11368736/dadeebfe8274/fphar-15-1425617-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d918/11368736/5a632c7f5402/fphar-15-1425617-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d918/11368736/c0d4785a2d9d/fphar-15-1425617-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d918/11368736/176bd22d6d3b/fphar-15-1425617-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d918/11368736/830090ba8105/fphar-15-1425617-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d918/11368736/5999911a6e47/fphar-15-1425617-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d918/11368736/dadeebfe8274/fphar-15-1425617-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d918/11368736/5a632c7f5402/fphar-15-1425617-g006.jpg

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[10]
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引用本文的文献

[1]
Management of ocular toxicity in patients with gynecologic cancer receiving novel antibody-drug conjugates: a narrative review.

Clin Transl Oncol. 2025-9-9

[2]
Immune checkpoint inhibitor-associated myocarditis and pericarditis: a pharmacovigilance study based on the FAERS database.

BMC Cancer. 2025-8-9

[3]
A disproportionality analysis of nervous system adverse events associated with disease-modifying therapies in multiple sclerosis: insights from the FDA adverse event reporting system (FAERS).

J Neurol. 2025-6-4

[4]
Corneal Findings in Patients Treated with Belantamab Mafodotin: A Prospective Case Series Focusing on Corneal Nerves.

Ophthalmol Ther. 2025-5-6

[5]
Phase I, First-in-Human Study of FOR46 (FG-3246), an Immune-Modulating Antibody-Drug Conjugate Targeting CD46, in Patients With Metastatic Castration-Resistant Prostate Cancer.

J Clin Oncol. 2025-5-20

[6]
Understanding the Toxicity Profile of Approved ADCs.

Pharmaceutics. 2025-2-14

本文引用的文献

[1]
Ocular toxicity associated with anti-HER2 agents in breast cancer: A pharmacovigilance analysis using the FAERS database.

Int J Cancer. 2024-5-1

[2]
Exploring the next generation of antibody-drug conjugates.

Nat Rev Clin Oncol. 2024-3

[3]
Antibody-Drug Conjugates and Ocular Toxicity.

J Ocul Pharmacol Ther. 2023-12

[4]
Ocular toxicities associated with antibody drug conjugates and immunotherapy in oncology: clinical presentation, pathogenesis, and management strategies.

Expert Opin Drug Saf. 2023

[5]
Antibody drug conjugates as targeted cancer therapy: past development, present challenges and future opportunities.

Arch Pharm Res. 2023-5

[6]
Hemophagocytic lymphohistiocytosis and disseminated intravascular coagulation are underestimated, but fatal adverse events in chimeric antigen receptor T-cell therapy.

Haematologica. 2023-8-1

[7]
Dupilumab-Induced, Tralokinumab-Induced, and Belantamab Mafodotin-Induced Adverse Ocular Events-Incidence, Etiology, and Management.

Cornea. 2023-4-1

[8]
Treatment-related adverse events of antibody-drug conjugates in clinical trials: A systematic review and meta-analysis.

Cancer. 2023-1-15

[9]
Strategies for Mitigating Antibody-Drug Conjugate Related Adverse Events for Precision Therapy.

Cancer J.

[10]
Gastrointestinal adverse events associated with semaglutide: A pharmacovigilance study based on FDA adverse event reporting system.

Front Public Health. 2022

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