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Reversible HER2 antibody-drug conjugate-induced ocular toxicity
Anushree Sharma1, Kamran M Riaz2, Mohsain S Gill3
1Medical Center Ophthalmology Associates, San Antonio, Tex.
Purpose:
To report 3 cases of reversible epitheliopathy induced by A166-a human epidermal growth factor receptor (HER2)-targeted antibody-drug conjugate (ADC) therapy for resistant HER2 tumours.
Methods:
Advanced HER2 tumour patients were enrolled in A166 phase I/II clinical trial using Bayesian logistic regression model dose escalation. Key exclusion criteria were ≥grade 2 (G2) corneal pathology, severe organ disease, and other cancer therapy within 4 weeks. Eye exams were performed at baseline, regularly scheduled intervals, and additionally upon A166-induced ocular symptoms. Topical therapy with autologous serum tears (ASTs) was implemented based on visual acuity, symptoms, and slit lamp exam. A166 was withheld if ≥G2 ocular toxicity developed; if status improved to ≤G1, A166 therapy was resumed. Visual acuity, corneal exam, and subjective comfort were recorded.
Results:
After ≥2 cycles of A166, 6 eyes of 3/23 enrolled patients developed whorl pattern epitheliopathy suggestive of limbal stem cell (LSC) dysfunction requiring cessation of A166 despite positive tumour response. Patients 1 and 3 received 3.6 mg/kg A166 dose, and patient 2 received 3.0 mg/kg. Topical steroids (2/4 eyes) failed to improve epitheliopathy. Adding ASTs improved vision, ocular comfort, and whorl pattern epitheliopathy in 6/6 eyes within 3 weeks. Patient 1 continues to improve on ASTs; patient 2 withdrew from the study; and patient 3 resumed A166 therapy.
Conclusion:
A166 precipitates LSC dysfunction-like epitheliopathy. Combination therapy including aggressive lubrication, withholding drug, and ASTs help reverse toxicity. Recognizing that ADC-induced epitheliopathy can respond to ocular management may enable cancer patients to continue lifesaving therapy.
Insights
A novel antibody-drug conjugate (ADC) therapy for HER2 tumors caused reversible eye toxicity. Prompt ocular management, including autologous serum tears (ASTs), helped patients maintain cancer treatment.
Area of Science:
- Ophthalmology
- Oncology
- Pharmacology
Background:
- HER2-targeted antibody-drug conjugates (ADCs) offer new therapeutic avenues for resistant HER2 tumors.
- Ocular toxicity is a potential concern with ADC therapies, necessitating careful monitoring and management.
Observation:
- Three patients receiving A166, an ADC targeting HER2, developed reversible epitheliopathy.
- This ocular toxicity, characterized by whorl pattern epitheliopathy, suggested limbal stem cell (LSC) dysfunction.
Findings:
- Discontinuation of A166 and subsequent treatment with autologous serum tears (ASTs) led to the reversal of epitheliopathy in all affected eyes.
- Aggressive lubrication and withholding the drug, combined with ASTs, proved effective in managing A166-induced ocular toxicity.
Implications:
- Recognizing and managing ADC-induced epitheliopathy is crucial for enabling patients to continue potentially life-saving cancer therapies.
- This study highlights the importance of a multidisciplinary approach involving ophthalmology and oncology for managing treatment-related adverse events.
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