Evaluation of prophylactic corticosteroid eye drop use in the management of corneal abnormalities induced by the antibody–drug conjugate mirvetuximab soravtansine

Academic Article

Abstract

  • © 2018 American Association for Cancer Research. Purpose: Reversible, low-grade ocular adverse events (AE) are associated with administration of mirvetuximab soravtansine, a folate receptor alpha (FRa)-targeted antibody–drug conjugate undergoing phase III clinical evaluation in platinum-resistant ovarian cancer. This study investigated the underlying mechanisms of ocular toxicity and evaluated primary prophylactic use of corticosteroid eye drops in patients receiving mirvetuximab soravtansine. Patients and Methods: Target expression in the human eye was determined by IHC. The ocular toxicity profile of mirvetuximab soravtansine was assessed preclinically using Dutch-Belted rabbits. In a phase I clinical study, patients with ovarian cancer were treated with 6 mg/kg mirvetuximab soravtansine intravenously once every 3 weeks, including one expansion cohort with corticosteroid eye drops administered daily for the first 10 days of each treatment c cle Results: FRa expression was absent from human corneal tissues. Ocular abnormalities in the rabbit eye appeared phe-notypically consistent with off-target effects on the cornea. Forty patients were enrolled in the expansion cohort. Reversible grade 1 or 2 blurred vision and keratopathy occurred in 16 (40%) and 12 (30%) patients, respectively; no grade 3/4 ocular events were observed. Compared with those patients who did not receive primary prophylaxis, corticosteroid eye drop use resulted in fewer dose reductions (5% vs. 15%) and none discontinued due to ocular AEs. Conclusions: Preclinical modeling was predictive of the corneal-related symptoms seen in some patients dosed with mirvetuximab soravtansine. Primary prophylactic use of topical corticosteroid eye drops resulted in a trend toward symptomatic improvement and a reduction in ocular AE-related dose modifications in patients treated with mirvetuximab soravtansine.
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    Author List

  • Matulonis UA; Birrer MJ; O'Malley DM; Moore KN; Konner J; Gilbert L; Martin LP; Bauer TM; Oza AM; Malek K
  • Start Page

  • 1727
  • End Page

  • 1736
  • Volume

  • 25
  • Issue

  • 6