AI Article Synopsis

  • The study investigates ocular adverse events (AE) associated with mirvetuximab soravtansine, a treatment for platinum-resistant ovarian cancer, focusing on prevention through corticosteroid eye drops.
  • It involves assessing FRα expression in the eye and evaluating preclinical ocular toxicity in rabbits, leading to a phase I clinical trial with patients treated alongside corticosteroid eye drops.
  • Results showed that about 40% of patients experienced mild, reversible ocular symptoms, and those using eye drops had fewer dose reductions, indicating the drops may help manage symptoms and reduce dose modifications.

Article Abstract

Purpose: Reversible, low-grade ocular adverse events (AE) are associated with administration of mirvetuximab soravtansine, a folate receptor alpha (FRα)-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 cycle.

Results: FRα expression was absent from human corneal tissues. Ocular abnormalities in the rabbit eye appeared phenotypically 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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Source
http://dx.doi.org/10.1158/1078-0432.CCR-18-2474DOI Listing

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