Dr Berkenstock on ADC-Related Ocular Toxicities in Cervical and Ovarian Cancers

Meghan K. Berkenstock, MD, associate professor, ophthalmology, Johns Hopkins Wilmer Eye Institute, discusses common ocular toxicities associated with the use of novel antibody-drug conjugates (ADCs), and the subsequent development of mitigation strategies for these treatment-related adverse effects (AE) in gynecologic cancers.

In September 2021, tisotumab vedotin-tftv (Tivdak) became the first ADC option to gain approval for patients with metastatic cervical cancer who experienced disease progression on or after chemotherapy. Prior to this approval, the agent’s related toxicities were identified through early, in-human studies, and remediation strategies were created, Berkenstock begins.

In the first-in-human phase 1/2 InnovaTV 201 (NCT02001623) trial, the implementation of mitigation strategies reduced the incidence of ocular treatment-related AEs (TRAEs) from 80% in 15 patients enrolled prior to implementation of these mitigation measures, to 60% in 40 patients enrolled after implementation. According to the subsequent phase 2 InnovaTV 204 trial (NCT03438396), the majority of ocular TRAEs observed with this agent were seen on the ocular surface, and included conjunctivitis, dry eye, and superficial punctate keratopathy/keratitis.

The mitigation strategy for tisotumab vedotin-related ocular toxicities involves the use of corticosteroids the day before infusion, as well as for 3 days after treatment initiation, Berkenstock continues. This is followed by the administration of artificial tears, Berkenstock says. Additionally, vasoconstrictor eye drops consisting of tetrahydrozoline or dilute brimonidine plus cold packs are given to patients before infusion, she adds. The resulting decrease in blood flow is thought to decrease off-target effects. Lastly, baseline eye examinations are performed prior to and throughout treatment, Berkenstock states. These measures allow clinicians to not only rapidly address any emerging toxicities but decrease off-target delivery of the agent’s payload to ocular tissue, Berkenstock explains. 

The ADC mirvetuximab soravtansine-gynx (Elahere) gained FDA approval in November 2022 for folate receptor alpha–positive, platinum-resistant ovarian cancer, Berkenstock says. Unlike tisotumab vedotin, toxicities seen with mirvetuximab soravtansine are primarily located in the cornea rather than on the ocular surface, she notes. Although the TRAE mitigation approach for this agent is different than that of tisotumab vedotin, it involves the same basic components, Berkenstock states. Patients will undergo ophthalmic evaluation with acute visits as needed, followed by the administration of both steroid and lubricating eye drops throughout treatment, she concludes.

Editor’s Note: Dr Berkenstock reports serving as a consultant for Eyepoint Pharmaceuticals.