Doctors treating platinum-resistant ovarian cancer have had few new drugs to reach for. In November 2022, the FDA gave accelerated approval to Elahere (mirvetuximab soravtansine-gynx), the first FDA-approved antibody-drug conjugate for platinum-resistant disease, according to drugmaker ImmunoGen.
It is meant for adults whose tumors are positive for folate receptor alpha (FRalpha), a protein found at high levels on the surface of ovarian cancer cells. These patients must have platinum-resistant epithelial ovarian, fallopian tube or primary peritoneal cancer and have received one to three earlier systemic treatment regimens. ImmunoGen describes the drug as first in class: an antibody aimed at FRalpha, linked to a cell-killing agent.
What the trial showed
Approval rested on SORAYA, a single-arm study of 106 patients whose tumors expressed high levels of FRalpha. All had been treated before, and each had received Avastin (bevacizumab) in at least one earlier regimen. By the investigator’s assessment, 31.7% of patients responded (95% confidence interval 22.9 to 41.6), and five had a complete response. The median duration of response was 6.9 months (95% confidence interval 5.6 to 9.7).
A single-arm trial has no comparison group, so these numbers cannot show whether patients live longer than they would on other treatment. That is why the approval is conditional. Continued approval may depend on a confirmatory trial, MIRASOL, which TechTarget reported was expected to yield results within the next year.
“Platinum-resistant ovarian cancer is a notoriously challenging disease to treat,” said Anna Berkenblit, ImmunoGen’s chief medical officer, noting that the FDA had approved no new therapy for this indication since 2014. Ursula Matulonis of the Dana-Farber Cancer Institute, a SORAYA co-principal investigator, pointed to the drug’s “impressive anti-tumor activity, durability of response, and overall tolerability.”
Side effects and warnings
Elahere carries a boxed warning for eye toxicity, including visual impairment, keratopathy, dry eye, photophobia, eye pain and uveitis. The safety review pooled data from three studies covering 464 patients who received at least one dose at 6 mg/kg adjusted ideal body weight, given intravenously.
Other common effects included fatigue, nausea, abdominal pain, peripheral neuropathy, diarrhea and constipation. Lab changes included higher liver enzymes (alanine aminotransferase and aspartate aminotransferase) and lower lymphocytes, albumin, magnesium, leukocytes, neutrophils and hemoglobin. TechTarget put ovarian cancer as the fifth leading cause of cancer deaths among women in the United States, according to the American Cancer Society.
Anyone with ovarian cancer who wonders whether this treatment applies to them, including whether their tumor tests positive for FRalpha, should talk to their doctor.
Sources
- FDA approves Elahere for the treatment of adult patients with folate receptor alpha positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer | medthority.com
- FDA Approves ELAHERE for Ovarian Cancer | TechTarget
