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Ashiyana Nariani, Marian Macsai-Kaplan; Corneal Toxicity of ABT-414, an investigational drug for Glioblastoma. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):1188.
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ABT-414 is an epidermal growth factor receptor (EGFR) monoclonal antibody conjugated to a microtubule toxin, currently in phase 1, multi-center trial to determine the safety and efficacy for glioblastoma (GBM).<br /> The current standard of care for GBM is surgical resection followed by radiation with adjuvant temozolomide. Despite treatment advances, median overall survival is 14-18 months. We report the incidence, prevalence, presentation and management of corneal toxicity in 12 patients who were enrolled in this trial.
A retrospective, observational clinical study was performed to review the corneal toxicity manifestations of 12 patients enrolled in the ABT-414 trial for glioblastoma. We also reviewed the current literature to assess the relationship between EGFR in the cornea and the mechanism of action of ABT-414, in order to determine the pathophysiology of ABT-414 ocular toxicity.
Four of the twelve GBM patients showed an objective radiographic response, two of whom achieved complete response. All 12 patients developed corneal toxicity (CT). CT symptoms included eye pain, photophobia, red eyes and decreased vision and varied in severity between patients. Four of the twelve patients are no longer in the study. Some have required a decrease in ABT-414 dosing due to the ocular effects. The CT presented with intra-epithelial corneal cysts, filamentary keratitis, corneal abrasions, whorl keratopathy, stromal opacities, and punctate epithelial erosions, all resembling advanced limbal stem cell dysfunction. All CT occurred while patients were treated with topical dexamethasone as part of the ABT-414 Trial, yet prednisolone acetate 1% was more effective in stabilizing and reversing the corneal toxicities.
ABT-414 has demonstrated promising preliminary results for patients with GBM. Yet, in this phase 1 trial, all patients developed CT resulting in debilitating ocular symptoms. To date, the corneal toxicities of ABT-414 have not been addressed in the literature. The pathophysiology is not well understood. Further studies into the relationship between EGFR in the cornea and the mechanism of action of ABT-414 and a protocol for the treatment or prevention of the corneal toxicity are required for this and other related antibody-drug conjugate treatments for GBM.
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