Ocular Toxicity Management for ADC Therapy in Breast and Lung Cancer: Mechanisms, Prevention, and Ophthalmology-Oncology Collaboration

In this expert discussion, Hope Rugo, MD; Neel Pasricha, MD; and Sarah Sunshine, MD explore ocular adverse events associated with antibody-drug conjugates (ADCs), examining pathophysiology, prevention, and multidisciplinary management. Dr. Pasricha explains that ocular toxicity appears to be an off-target effect rather than antibody-mediated binding to corneal cells, with severity varying by agent. For example, telisotuzumab vedotin and datopotamab deruxtecan (Dato-DXd) exhibit high incidence but typically low-grade events, whereas belantamab mafodotin shows both high incidence and greater severity. The characteristic pattern begins peripherally where blood vessels meet the cornea and migrates centrally, suggesting a primarily blood-based mechanism, although ADC payload is also detected in tears.

Key considerations include establishing ophthalmology-oncology collaboration before initiating therapy, baseline ophthalmologic assessments for certain ADCs, and educating patients on early warning signs and when to seek urgent evaluation. Dr. Sunshine emphasizes that early identification enables timely intervention through treatment holds or dose modifications.

The panel notes that current supportive therapies, such as preservative-free artificial tears and topical agents, do not address the underlying pathophysiology, highlighting the need for ongoing research into prevention strategies. Throughout, the speakers stress multidisciplinary coordination and clear patient communication to balance ocular safety with the clinical benefits of ADC therapy.