Mirvetuximab soravtansine-gynx, an antibody drug conjugate, has received accelerated approval for platinum-resistant ovarian cancer. The prescribing label comes with warnings for visual toxicities, pneumonitis, and peripheral neuropathy.
The FDA has granted mirvetuximab soravtansine-gynx (Elahere) accelerated approval on the indication of folate receptor alpha (Frα)– positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer. Patients may have been treated with 1 to 3 prior therapies to be eligible for treatment.1-3
The accelerated approval is backed by findings from the phase 3 SORAYA trial (NCT04296890), which showed that patients who received mirvetuximab soravtansine achieved an objective response rate of 31.7% (95% CI, 22.9%-41.6%), including 5 complete responses. In addition, the median duration of response was 6.9 months (95% CI, 5.6%-9.7%).
The FDA has also approved the companion diagnostic, VENTANA FOLR1 (FOLR-2.1), to help identify patients for whom this treatment is suitable. Testing can be done on fresh or archived tissue, and patients can be tested at diagnosis to determine if this treatment would be appropriate at the time of platinum resistance.
"The approval of ELAHERE is significant for patients with FRα-positive platinum-resistant ovarian cancer, which is characterized by limited treatment options and poor outcomes," Ursula Matulonis, MD, chief of the Division of Gynecologic Oncology at the Dana-Farber Cancer Institute, professor of medicine at the Harvard Medical School, and SORAYA co-principal investigator, stated in a press release. “ELAHERE’s impressive anti-tumor activity, durability of response, and overall tolerability observed in SORAYA demonstrate the benefit of this new therapeutic option, and I look forward to treating patients with ELAHERE."
In the United States, ovarian cancer represents the leading cause of death from gynecologic cancers. Approximately 20,000 patients are diagnosed with this disease, and 13,000 die from it, annually.
The current standard of care for ovarian cancer is surgery followed by platinum-based chemotherapy. However, most patients eventually develop platinum-resistant disease, and effective treatment options in this disease setting are limited. Many patients end up receiving single-agent chemotherapies that yield low response rates, short response times, and high toxicity burdens.
The SORAYA trial was a single-arm study which enrolled 106 patients with platinum-resistant ovarian cancer and Frα-positive tumors. All patients were allowed to have had at least 3 prior lines of therapy, and all were required to have received bevacizumab. Mirvetuximab soravtansine is an antibody-drug conjugate directed against Frα, a cell surface protein which is highly expressed in ovarian cancer. The new agent is the first antibody-drug conjugate to be approved in this setting.
The recommended dose is 6 mg/kg adjusted ideal body weight every 3 weeks.
Mirvetuximab soravtansine comes with a boxed warning for ocular toxicity, including visual impairment, keratopathy, dry eye, photophobia, eye pain, and uveitis. In the trial, 61% of patients experienced an ocular toxicity, 9% of which were grade 3. The median time to first ocular adverse event was 1.2 months (range, 0.03-12.9).
Prior to treatment with mirvetuximab soravtansine, patients should receive an ophthalmic exam, including visual acuity and slit lamp exam. These exams should continue every other cycle for the first 8 cycles and then as clinically indicated.
It is recommended to premedicate patients with lubrication and ophthalmic topical steroids during treatment. In addition, patients should be advised to avoid contact lenses, unless directed by a healthcare providers. For patients who experience ocular toxicity, prophylactic artificial tears and ophthalmic topical steroids may be administered. Treatment should be withheld until toxicities improve. If grade 4 ocular toxicities occur, treatment should be discontinued.
Patients who receive mirvetuximab soravtansine are also at an increased risk pf pneumonitis and peripheral neuropathy. These adverse effects (AEs) occurred in 10% and 36% of treated patients, respectively. Patients should be monitored for signs of pulmonary symptoms, or neuropathy. If pulmonary signs develop, infectious, neoplastic, and other causes for symptoms should be excluded through appropriate investigations.
Overall, serious AEs occurred in 31% of patients. The most common AEs include intestinal obstruction (8%), ascites (94%), infection (3%), and pleural effusion (3%). Two percent of patients experienced fatal AEs. The most common any grade AEs included vision impairment, fatigue, increased aspartate aminotransferase, nausea, increased alanine aminotransferase, keratopathy, abdominal pain, decreased lymphocytes, peripheral neuropathy, diarrhea, decreased albumin, constipation, increased alkaline phosphatase, dry eye, decreased magnesium, decreased leukocytes, decreased neutrophils, and decreased hemoglobin.
In addition, 20% of patients needed dose reduction because of toxicities. The toxicities which contributed to dose reductions included intestinal obstruction (2%) and thrombocytopenia (2%). One patient discontinued because of visual impairment.
Moreover, 39% of patients required dose delays. The AEs which were responsible for dose delays were visual impairment (15%), keratopathy (11%), neutropenia (6%), dry eye (5%), cataracts (3%) and increased gamma-glutamyltransferase (3%).
Continued approval will be contingent on the findings from the phase 3 MIRASOL trial (NCT04209855), a confirmatory randomized trial designed to confirm the findings of SORAYA. The trial is fully enrolled and top-line data are anticipated in early 2023.