Reversible HER2 antibody-drug conjugate–induced ocular toxicity

Anushree Sharma, Kamran M. Riaz, Mohsain S. Gill, Amita Patnaik, Susanna V. Ulahannan, Judy S. Wang, Dan S. Gombos, Qiuqing Ang, Dragan Cicic, Gregory R. Bergonio, Cong Zhang, Barbara M. Wirostko

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)118-126
Number of pages9
JournalCanadian Journal of Ophthalmology
Issue number2
StatePublished - Apr 2022


  • Bayes Theorem
  • Clinical Trials, Phase I as Topic
  • Clinical Trials, Phase II as Topic
  • Cornea/pathology
  • Humans
  • Immunoconjugates/metabolism
  • Tears/metabolism
  • Toxic Optic Neuropathy

ASJC Scopus subject areas

  • Ophthalmology


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