TY - JOUR
T1 - Reversible HER2 antibody-drug conjugate–induced ocular toxicity
AU - Sharma, Anushree
AU - Riaz, Kamran M.
AU - Gill, Mohsain S.
AU - Patnaik, Amita
AU - Ulahannan, Susanna V.
AU - Wang, Judy S.
AU - Gombos, Dan S.
AU - Ang, Qiuqing
AU - Cicic, Dragan
AU - Bergonio, Gregory R.
AU - Zhang, Cong
AU - Wirostko, Barbara M.
N1 - Publisher Copyright:
© 2021 Canadian Ophthalmological Society
PY - 2022/4
Y1 - 2022/4
N2 - 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.
AB - 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.
KW - Bayes Theorem
KW - Clinical Trials, Phase I as Topic
KW - Clinical Trials, Phase II as Topic
KW - Cornea/pathology
KW - Humans
KW - Immunoconjugates/metabolism
KW - Tears/metabolism
KW - Toxic Optic Neuropathy
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U2 - 10.1016/j.jcjo.2021.02.028
DO - 10.1016/j.jcjo.2021.02.028
M3 - Article
C2 - 33727105
AN - SCOPUS:85103058838
SN - 0008-4182
VL - 57
SP - 118
EP - 126
JO - Canadian Journal of Ophthalmology
JF - Canadian Journal of Ophthalmology
IS - 2
ER -