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Ocular adverse events associated with antibody-drug conjugates in oncology: a pharmacovigilance study based on FDA
KaiLi Mao1, Ping Chen1, HuaYu Sun1
1Department of Pharmacy, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Quzhou, Zhejiang, China.
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.
Insights
Antibody-drug conjugates (ADCs) are linked to significant ocular toxicity, including keratopathy and vision loss. This analysis highlights the risks associated with specific ADCs, emphasizing the need for careful monitoring in cancer patients.
Area of Science:
- Oncology
- Ophthalmology
- Pharmacovigilance
Background:
- Antibody-drug conjugates (ADCs) are increasingly used in cancer therapy.
- Ocular toxicity associated with ADCs is a significant concern that is often underestimated.
- Comprehensive analysis of ADC-related ocular adverse events is crucial for patient safety.
Purpose of the Study:
- To comprehensively and comparatively analyze the risk of ocular toxicity associated with various ADCs.
- To identify specific ADCs with higher susceptibility to causing ocular adverse events.
- To evaluate the time to onset of ocular toxicity for different ADCs.
Main Methods:
- Utilized the FDA Adverse Event Reporting System (FAERS) database from Q3 2011 to Q3 2023.
- Analyzed clinical characteristics of ADCs-related ocular adverse events (AEs).
- Employed proportional analysis and Bayesian approach for signal detection and evaluated time to onset.
Main Results:
- Identified 1,246 cases of ocular AEs attributed to ADCs, with significant toxicity signals for belantamab mafodotin, brentuximab vedotin, enfortumab vedotin, mirvetuximab soravtansine, sacituzumab govitecan, trastuzumab deruxtecan, and trastuzumab emtansine.
- Belantamab mafodotin, trastuzumab emtansine, and mirvetuximab soravtansine (microtubule inhibitors) showed higher ocular toxicity susceptibility.
- Common AEs included keratopathy, reduced visual acuity, dry eye, night blindness, blurred vision, photophobia, foreign body sensation, ocular toxicity, and punctate keratitis. Onset times varied from 21 days (sacituzumab govitecan) to 223 days (trastuzumab deruxtecan).
Conclusions:
- ADCs pose a notable risk of ocular toxicity in cancer patients, potentially leading to severe outcomes.
- Integrating FAERS data with other sources is vital for ongoing monitoring of ADC-induced ocular toxicity, especially with new ADC approvals.
- Novel ocular toxicity signals were identified, necessitating further research for validation and improved patient management.
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