Mirvetuximab soravtansine data ‘practice changing’ for subset of women with ovarian cancer
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Key takeaways:
- The antibody-drug conjugate conferred a 33% reduction in hazard for death vs. chemotherapy.
- The results position mirvetuximab soravtansine-gynx as a new standard of care, according to researchers.
CHICAGO — Mirvetuximab soravtansine-gynx extended survival of women with platinum-resistant ovarian cancer and high folate receptor-alpha expression, according to a study that compared the agent with investigator’s choice of chemotherapy.
The antibody and microtubule inhibitor conjugate is the first novel therapy to show a survival benefit in a randomized phase 3 study among this patient population, according to Kathleen N. Moore, MD, MS, associate director of clinical research and co-director of the cancer therapeutics program of Stephenson Cancer Center at University of Oklahoma College of Medicine.
“We believe these data are practice changing and position mirvetuximab as the new standard of care for patients with folate receptor alpha-positive, platinum-resistant ovarian cancer,” Moore said during a presentation of the findings at ASCO Annual Meeting.
Background, methodology
Mirvetuximab soravtansine-gynx (Elahere, ImmunoGen) targets folate receptor alpha, which is overexpressed “almost ubiquitously” in high-grade serous ovarian cancer and highly expressed in about 35% of cases, Moore said. The agent received accelerated approval in November — based on results of the phase 3 SORAYA trial — for women with folate receptor alpha-positive, platinum-resistant epithelial ovarian, fallopian tube or primary peritoneal cancer who received one to three previous systemic treatment regimens.
The confirmatory MIRASOL trial assessed the agent compared with standard-of-care chemotherapy among 453 women with advanced platinum-resistant ovarian cancer and high folate receptor alpha expression. PFS served as the primary endpoint, with objective response rate per investigator assessment, OS and patient-reported outcomes as key secondary endpoints.
Median follow-up was 13.1 months.
Results
Mirvetuximab soravtansine conferred a 35% reduction in risk for disease progression or death compared with chemotherapy, with median PFS of 5.62 months vs. 3.98 months (HR = 0.65; 95% CI, 0.52-0.81). The mirvetuximab soravtansine group also had a higher ORR (42% vs. 16%), including 12 complete responses vs. none in the chemotherapy group, and a 33% reduction in hazard for death (HR = 0.67; 95% CI, 0.5-0.89). Moore reported median OS of 16.46 months with mirvetuximab soravtansine vs. 12.75 months with chemotherapy.
PFS and ORR by blinded independent central review mirrored results by investigator assessment, Moore said.
Researchers observed a consistent benefit with the antibody-drug conjugate regardless of previous treatment with bevacizumab (Avastin, Genentech). Mirvetuximab soravtansine also appeared tolerable compared with chemotherapy, with fewer grade 3 or greater treatment-related adverse events (42% vs. 54%), serious adverse events (24% vs. 33%) and discontinuations due to treatment-related adverse events (9% vs. 16%).
The key safety signal with mirvetuximab soravtansine is ocular toxicity, including keratopathy, dry eye and blurred vision, the latter of which can occur in 42% of patients, Moore said.
“This is primarily low grade, and there are preventive and mitigation strategies that allow patients to have this as a reversible toxicity and [continue] the medication to maximal benefit,” she said.
Perspective
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Maurie Markman, MD
Impressive advances in the therapeutic armamentarium have been employed in the management of advanced ovarian cancer, including most prominently the delivery of bevacizumab as a component of treatment for primary, recurrent platinum-sensitive and platinum-resistant disease and the use of several anti-[poly (ADP-ribose) polymerase] PARP agents as a maintenance strategy. Added to this list is mirvetuximab soravtansine, a novel antibody-cytotoxic conjugate directed to the folate receptor alpha, which has been shown to be present in the large majority of epithelial ovarian cancers.
Although the availability of this agent in the management of platinum-resistant ovarian cancer should be loudly applauded, as is often the case when a novel strategy enters the realm of routine clinical practice, there are remaining clinically relevant questions associated with its use. Two points to be briefly mentioned are the relative efficacy of mirvetuximab soravtansine compared with chemotherapy plus bevacizumab (also FDA approved in this clinical setting) and the concern for the unique ocular toxicity reported in clinical trials. But like most issues in cancer management, these will likely be addressed and hopefully answered in future trials and real-world experience with this important new agent.
City of Hope
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Moore K, et al. Abstract LBA5507. Presented at: ASCO Annual Meeting; June 2-6, 2023; Chicago.
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