On March 22, 2024, mirvetuximab soravtansine-gynx (Elahere) was granted regular approval for adult patients with folate receptor–alpha (FRα)-positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer who have received one to three prior systemic treatment regimens.1 The agent received accelerated approval for this indication in November 2022.
Supporting Efficacy Data
Approval was supported by the open-label Study 0416 (MIRASOL; ClinicalTrials.gov identifier NCT04209855), in which 453 patients were randomly assigned to receive mirvetuximab soravtansine at 6 mg/kg every 3 weeks or investigator’s choice of chemotherapy (paclitaxel, pegylated liposomal doxorubicin, or topotecan) until disease progression or unacceptable toxicity.
The median overall survival was 16.5 months (95% confidence interval [CI] = 14.5–24.6 months) in the mirvetuximab soravtansine group vs 12.7 months (95% CI = 10.9–14.4 months) in the chemotherapy group (hazard ratio [HR] = 0.67, 95% CI = 0.50–0.88, P = .0046). Median investigator-assessed progression-free survival was 5.6 months (95% CI = 4.3–5.9 months) vs 4.0 months (95% CI = 2.9–4.5 months) for the respective arms (HR = 0.65, 95% CI = 0.52–0.81, P < .0001). Overall response rates were 42% (95% CI = 36%–49%) and 16% (95% CI = 12%–22%), respectively (P < .0001).
How It Is Used
The recommended mirvetuximab soravtansine dose is 6 mg/kg adjusted ideal body weight once every 3 weeks until disease progression or unacceptable toxicity. Its use requires the presence of FRα tumor expression detected with U.S. Food and Drug Administration–approved test.
Product labeling provides instructions on premedication for infusion-related reactions, nausea, and vomiting and premedication for ocular toxicity. Labeling provides instructions on dose modification, including dose reduction, for adverse reactions including keratitis/keratopathy, uveitis, pneumonitis, peripheral neuropathy, and infusion-related reactions/hypersensitivity, and hematologic toxicity. Its use should be avoided in patients with moderate or severe hepatic impairment. Patients receiving strong CYP3A4 inhibitors (eg, clarithromycin, diltiazem, erythromycin) should be monitored closely for mirvetuximab soravtansine–related adverse reactions.
Safety Profile
In MIRASOL, the most common adverse events of any grade in the mirvetuximab soravtansine group were fatigue (47% vs 41% in chemotherapy group), blurred vision (45% vs 3%), keratopathy (37% vs 0%), peripheral neuropathy (37% vs 23%), abdominal pain (34% vs 23%), musculoskeletal pain (31% vs 28%), dry eye (29% vs 5%), diarrhea (29% vs 17%), constipation (27% vs 19%), and nausea (27% vs 29%). The most common grade 3 or 4 adverse events in the mirvetuximab soravtansine group were keratopathy (11%) and blurred vision (9%). The most common grade 3 or 4 laboratory abnormality was decreased lymphocytes (3%).
Serious adverse events occurred in 24% of the mirvetuximab soravtansine group, most commonly intestinal obstruction (5%), abdominal pain (3%), and pleural effusion (3%). Adverse events led to discontinuation of treatment in 9% of patients, most commonly pneumonitis (2%). Fatal adverse events occurred in 3% of patients, including intestinal obstruction, dyspnea, neutropenic sepsis, cardiopulmonary failure, respiratory failure, ischemic stroke, and pulmonary embolus.
Mirvetuximab soravtansine has a boxed warning for ocular toxicity. It also has warnings/precautions for pneumonitis, peripheral neuropathy, and embryofetal toxicity. Patients should be advised not to breastfeed while receiving mirvetuximab soravtansine.
REFERENCE
1. Elahere (mirvetuximab soravtansine-gynx) injection, for intravenous use, prescribing information, ImmunoGen, Inc, March 2024. Available at https://www.elahere.com. Accessed April 5, 2024.
