Mitigation and management strategies for ocular events associated with tisotumab vedotin.

Tisotumab vedotin is a tissue factor-directed antibody-drug conjugate developed for treatment of recurrent or metastatic cervical cancer (r/mCC). In the pivotal phase 2 study innovaTV 204, 101 r/mCC patients received tisotumab vedotin. 138 ocular treatment-related AEs (TRAEs), predominantly Grade 1 or 2, were observed in 54 (53%) patients. The most common ocular TRAEs were conjunctivitis (26 patients [26%]), dry eye (23 patients [23%]), and keratitis (11 patients [11%]). Observed ocular TRAEs are hypothesized to be conjunctival and inflammatory in nature, resulting in signs and symptoms readily recognizable by patients and healthcare providers. Generally, ocular TRAEs were manageable with ophthalmic care (prophylactic and symptom management) and dose modifications. Of 138 ocular TRAEs, 118 (86%) resolved within 30 days after last dose of tisotumab vedotin. Median time to resolution was 0.7 months (interquartile range: 0.3-1.6). To help reduce the risk of ocular AEs, an eye care plan based on clinical trial experience was developed. This encompasses an oncology care team partnering with an eye care provider, incorporates eye exams at baseline (per trial mitigation measures) and prior to each dose, includes eye drops and cold packs, avoids contact lens use, and advises prompt referral for new or worsening ocular signs and symptoms. Moreover, dose modification guidelines have been developed to manage potential ocular AEs. Ocular AEs will require patient management strategies that may be new to oncology teams. Oncologists should become familiar with symptoms that typically arise, and eye care providers should be an integral part of the comprehensive care team treating patients receiving tisotumab vedotin. With diligent monitoring for early signs and symptoms, careful adherence to required eye care, pharmacologic intervention when ocular AEs arise, and dose modifications when needed, ocular AEs can be detected early and symptoms can be alleviated before any impact on vision, to ultimately help patients stay on therapy.
Competing Interests: Declaration of Competing Interest Dr. Kim reports consulting/advisory roles for Seagen, ImmunoGen, Abbvie, Astellas, CytomX, and Zymeworks outside the submitted work. Dr. Ursell reports travel grants & fees from Alcon, Medisoft & Essilor outside the submitted work. Dr. Coleman reports grants and personal fees from AstraZeneca, grants from Merck, personal fees from GSK, grants and personal fees from Clovis, grants and personal fees from Genmab, grants and personal fees from Roche/Genentech, grants and personal fees from Janssen, personal fees from Agenus, personal fees from Regeneron, and personal fees from OncoQuest outside the submitted work. Dr. Monk reports personal fees from Agenus, Akeso Bio, Aravive, AstraZeneca, Clovis, Easai, Elevar, EMD Merck, Genmab/Seagen, GOG Foundation, Gradalis, ImmunoGen, Karyopharm, Iovance, Merck, Mersana, Novocure, Myriad, Pfizer, Puma, Regeneron, Roche/Genentech, Sorrento, TESARO/GSK, US Oncology Research, and VBL outside the submitted work. Dr. Vergote reports research funding from Amgen (Europe) GmbH and Roche and personal fees from AstraZeneca, Deciphera Pharmaceuticals, Elevar Therapeutics, F Hoffman-La Roche Ltd., Genmab, GSK, Immunogen Inc., Jazzpharma, Mersana, MSD, Novocure, Oncoinvent AS, and Sotio a.s. outside the submitted work.
(Copyright © 2022. Published by Elsevier Inc.)