Ocular Side Effects Common in Real-World Study of Cancer Tx

CHICAGO — A real-world study of the ocular side effects of the gynecological cancer treatment mirvetuximab (Elahere) has found more than two of three women taking the drug experienced some type of corneal toxicity, surpassing rates reported in previous studies.

The study, by researchers at Byers Eye Institute of Stanford University, Stanford, California, was a retrospective analysis of 36 eyes of 18 women who received mirvetuximab for FR-alpha–positive, platinum-resistant primary ovarian cancer.

Drug-related corneal toxicity occurred in 69% of eyes, with corneal toxicity mostly occurring after the second cycle of treatment with the antibody drug conjugate (ADC), Filippos Vingopoulos, MD, an ophthalmologist at Byers Eye Institute, reported in a poster presented at the 2024 annual meeting of the American Academy of Ophthalmology.

“We found that mirvetuximab-associated corneal toxicity is even more common in real-world practice than in the clinical trials,” Vingopoulos told Medscape Medical News. “It mainly manifests as paracentral corneal subepithelial cystic deposits that resolve with high potency topical corticosteroids and dose reduction or delay, with restoration of clear cornea and return to baseline vision in most cases.”

Patients Need Ongoing Eye Care

Patients taking mirvetuximab should be monitored regularly by an eye-care provider, Vingopoulos said. “The recommendation includes a baseline ophthalmology visit prior to starting on mirvetuximab, topical corticosteroid drops 1 day before up until 8 days after every cycle, and follow-up eye exams about every 6 weeks during the first eight cycles of treatment,” he said.

The prescribing information for mirvetuximab carries a black box warning about potential ocular side effects.

Mirvetuximab, a first-in-class ADC, received accelerated approval in 2022 from the US Food and Drug Administration for treatment of FR-alpha positive, platinum-resistant epithelial ovarian, fallopian tube, or peritoneal cancer. Full approval for the same indication came earlier this year.

Patients in the Stanford study had an average follow-up of 5.5 months and received 5.8 infusions (±2.1 infusions). Eight eyes (22%) had mild and 17 (47%) had moderate to severe ocular toxicity.

With regards to specific types of corneal toxicity, 24 eyes (66.6%) had subepithelial deposits, three (8.3%) had corneal haze, one eye had filamentous keratitis, and 20 eyes (55.5%) had decreased visual acuity, Vingopoulos said.

Management of the ocular side effects varied. Twelve patients (33.3%) had their mirvetuximab dose reduced, and eight (22.2%) had their infusions delayed. Twenty-five eyes (69.4%) were treated with high-potency topical corticosteroids for corneal problems, but none discontinued mirvetuximab therapy.

“Having good communication between eye-care providers and the oncologists, who are the ones administering this drug, is very important because you want to monitor for these adverse events that are known to happen, and if they do happen right now, the only effective known therapy is to do an ADC dose disruption of some kind,” Vingopoulos said. In severe cases, the mirvetuximab may be stopped.

He noted these rates were higher than those reported in the pivotal clinical trials. In the postmarket SORAYA study, 52% of patients taking mirvetuximab had blurred vision or keratopathy, and 11% required a dose reduction. In the phase 3 MIRASOL trial, 56% of all mirvetuximab-treated patients had nonspecific ocular adverse events and 14% had moderate to severe side effects.

Not all patients in the Stanford study fully recovered from the ocular side effects. Twenty of 25 eyes (80%) had complete resolution of corneal toxicity, and 13 of 20 (65%) returned to their baseline visual acuity.

“Our early real-world case series reaffirms the mirvetuximab-associated corneal toxicity reported in the phase 3 clinical trials and suggests good response to high-dose topical corticosteroids,” Vingopoulos reported.

The study, despite its small size and retrospective design, is notable because it provides real-world data on the ocular side effects of mirvetuximab and did not receive any industry funding, according to Neel Pasricha, MD, a surgeon and external ocular disease specialists at the University of California — San Francisco in San Francisco, California, who studies ocular toxicity of ADC drugs.

“With these ADC drugs, when they come to market, these are the types of studies that can really be informative on what are the ocular adverse events and what is the actual meaning of them to patients,” Pasricha told Medscape Medical News.

The rate of corneal toxicity in the Stanford study falls in line with other postmarket studies of mirvetuximab, although “slightly higher” than what has been previously reported, he said.

The Stanford study also was noteworthy because it reported how many patients had their doses of mirvetuximab either reduced or delayed, he said. But dose disruption does not mean monitoring ocular side effects ends, Pasricha added.

“Just because the ADC is either stopped, delayed or reduced, patients still have the corneal toxicity that can linger for a few weeks up to months after stopping or delaying the ADC, so it’s not an immediate effect,” he said. “There’s still ongoing follow-up with the eye-care team.”

No data are available to help identify which patients are more at risk for ocular side effects, Pasricha added.

The study received no outside funding. Vingopoulos had no relevant disclosures. Pasricha disclosed financial relationships with Sanofi and AstraZeneca.

Richard Mark Kirkner is a medical journalist based in the Philadelphia area.