Mirvetuximab soravtansine plus bevacizumab may benefit women with recurrent ovarian cancer and high folate receptor alpha (FRα) expression, regardless of platinum sensitivity. In a phase I/II trial, the combination elicited an objective response rate of 64% and a median progression-free survival of 10.6 months in patients with FRα–high tumors.
The antibody–drug conjugate (ADC) mirvetuximab soravtansine (IMGN853; Immunogen) plus the angiogenesis inhibitor bevacizumab (Avastin; Genentech) may benefit women with recurrent ovarian cancer and high folate receptor alpha (FRα) expression, regardless of their sensitivity to platinum-based chemotherapy. In a phase I/II trial, a high percentage of patients responded to the combination, and responses were lasting. Findings were presented at the American Society of Clinical Oncology (ASCO) 2021 Annual Meeting, June 4–8.
As treatment for ovarian cancer has improved, patients are undergoing more rounds of platinum-based chemotherapy and living longer, meaning that more women will eventually develop recurrent disease insensitive to platinum-based therapies.
Mirvetuximab soravtansine targets FRα, which is overexpressed in up to 90% of ovarian cancers. The drug's cytotoxic payload is DM4, a maytansinoid that destroys tubulin in cancer cells, causing them to die. In earlier trials, the agent “demonstrated significant activity in platinum-resistant ovarian cancer,” as a monotherapy and in combination with bevacizumab, said David O'Malley, MD, of The Ohio State University College of Medicine in Columbus.
At the ASCO meeting, O'Malley presented results from a phase I/II trial testing mirvetuximab soravtansine plus bevacizumab in 60 patients who had previously received a median of two therapies: 41 with advanced ovarian cancer, 15 with primary peritoneal cancer, and four with fallopian tube cancer. All of them had received taxanes and platinum-based agents before the trial, and about half had developed platinum-resistant disease; about 40% had been given bevacizumab.
Patients were stratified into medium and high FRα expression groups based on immunohistochemistry. Those with medium FRα expression had an objective response rate (ORR) of 33%, a median progression-free survival (PFS) of 5.4 months, and a median duration of response (DoR) of 8.3 months. In contrast, those with high FRα expression had an ORR of 64%, a median PFS of 10.6 months, and median DoR of 11.8 months. Within the FRα expression–high group, platinum-resistant patients had an ORR of 59%, a median PFS of 9.7 months, and a median DoR of 9.4 months, versus 69%, 13.3 months, and 12.7 months, respectively, in platinum-sensitive patients. “These deep responses are rapid and durable” in patients with high FRα expression, O'Malley said.
Side effects were mostly low-grade and manageable. The most common grade 3 and 4 adverse events were hypertension and neutropenia, seen in 17% and 13% of patients, respectively. Overall, 30% of patients discontinued one or both therapies due to side effects, but O'Malley noted that discontinuation occurred after a median of 13 treatment cycles.
“The combination … was highly active in a broad population of recurrent cancer patients with high folate receptor alpha expression,” O'Malley said, adding that the strong results regardless of platinum resistance are “very exciting and, I think, a very compelling finding.” The data support mirvetuximab soravtansine as the “partner of choice” for bevacizumab, O'Malley concluded, suggesting that the combination should be developed further.
The trial is “a great demonstration in terms of activity of mirvetuximab [soravtansine] and bevacizumab in the context of folate receptor alpha … in a platinum-agnostic group of patients,” said discussant Amit Oza, MD, of Princess Margaret Cancer Centre in Toronto, Ontario. The results were intriguing given that many patients had already received taxanes and bevacizumab, he added. “It does perhaps lead to the encouraging possibility that you can move beyond weekly paclitaxel and bevacizumab, perhaps, in recurrence,” he said, “but this needs to be looked at in a prospective manner.” –Catherine Caruso