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.

 Dr Berkenstock reports serving as a consultant for Eyepoint Pharmaceuticals.

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Meghan K. Berkenstock, MD, discusses common ocular toxicities associated with the use of novel antibody-drug conjugates, and the subsequent development of mitigation strategies for these treatment-related adverse effects in gynecologic cancers.


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 the management of antibody-drug conjugate (ADC)–related ocular toxicities in gynecologic cancers.

As the use of ADCs in ovarian, cervical, and other gynecologic cancers increases, there is growing need for effective mitigation strategies for treatment-related adverse effects (TRAEs), specifically high-grade ocular toxicities, Berkenstock says. Common ocular TRAEs include conjunctivitis, ulcerative keratitis, dry eye, and keratopathy/keratitis. Many of these ocular toxicities occur because of off-target delivery of the agent’s payload, which can lead to a loss of epithelial cells on the cornea, Berkenstock explains. Reduction in the number of epithelial cells can lead to infection or thinning of the cornea, she adds.

The management of these toxicities in clinical practice involves substantial coordination of patient care and communication between ophthalmologists and oncologists, Berkenstock emphasizes. Many patients take time to adjust to the use of prophylactic steroid eye drops, which should be given prior to and 72 hours after infusion with tisotumab vedotin-tftv (Tivdak) or through day 10 of treatment with mirvetuximab soravtansine-gynx (Elahere), Berkenstock states. Clinicians not only issue the original prescription for these steroids, but remind the patient to regularly administer them, Berkenstock says. Morevoer, they can monitor the patient for signs of ocular toxicities, such as reduced visual acuity, blurred vision, light senstivity, redness, dryness and irritation. The performance of a regular baseline eye exam prior to each ADC infusion is also vital to toxicity management, Berkenstock notes.

The early referral of patients to ophthalmologists in the event of conjuctival or corneal inflammation can also help prevent the development of severe ocular AEs, Berkenstock says. This also supports ongoing efforts to educate ophthalmologists about ADCs, and familiarize them with the AE grading scale for ocular examinations, Berkenstock concludes.

Berkenstock reports serving as a consultant for Eyepoint Pharmaceuticals.

Meghan K. Berkenstock, MD, discusses the management of antibody-drug conjugate-related ocular toxicities in gynecologic cancers.



Meghan K. Berkenstock, MD

Articles

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

Dr Berkenstock on the Mitigation of ADC-related Ocular Toxicities in Gynecologic Cancers