The antibody-drug conjugate (ADC) mirvetuximab soravtansine (Elahere) could become a new standard of care for some patients with ovarian cancer, specifically those whose tumors are folate receptor-alpha (FR-alpha) positive and also platinum-resistant..
The product demonstrated “clinically meaningful antitumor activity” in this population, with a median overall survival of 15 months, said researchers reporting new data from the SORAYA trial. At 24 months, 37% of patients remained alive.
The objective response rate (ORR) for the entire cohort was 32.4%. This response rate compares favorably to those for other single-agent therapies (which is around 4%-13%), and the response rates were consistent regardless of the number of prior lines of therapy or previous exposure to PARP inhibitors, noted lead author Robert L. Coleman, MD, US Oncology Research, Texas Oncology, The Woodlands, Texas.
“These results position mirvetuximab to become a practice-changing, biomarker-driven, standard of care treatment option for patients with folate receptor, alpha–positive, platinum-resistant ovarian cancer,” he concluded.
“More that 90% of ovarian cancer overexpresses folate receptor alpha,” he noted. Coleman presented the findings at the Society of Gynecologic Oncology (SGO) 2023 Annual Meeting on Women’s Cancer.
Mirvetuximab soravtansine was granted accelerated approval this past November by the US Food and Drug Administration for patients with FR-alpha–positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have progressed on one to three prior lines of systemic therapy. It is a first-in-class ADC that is comprised of an FR-alpha-binding antibody, cleavable linker, and maytansinoid DM4, a potent tubulin-targeting agent.
Approached for comment, Gina Mantia-Smaldone, MD, associate professor, Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, said: “The results of the SORAYA study helped to establish mirvetuximab soravtansine as a new FDA-approved treatment option for platinum-resistant ovarian cancer.,” said
“The results presented by Dr Coleman indicate a clinical benefit in patients with high folate-receptor-alpha tumor expression,” she added. “These results also indicate that patients may benefit from mirvetuximab earlier in their treatment plans, including with platinum-sensitive disease.”
SORAYA is a global, single-arm, phase 3 study that evaluated mirvetuximab soravtansine in adults with FR-alpha, platinum-resistant, high-grade, serous epithelial ovarian, primary peritoneal, or fallopian tube cancer.
Of the 106 patients enrolled in SORAYA, 55 had received three prior lines of therapy, 51 had received one or two prior lines, and 37% of patients had received their prior treatment in the platinum-resistant setting. All patients had received prior bevacizumab (Avastin), and 16% had prior bevacizumab exposure in the platinum-resistant setting.
Patients received intravenous mirvetuximab at 6 mg/kg, adjusted ideal body weight, on day 1 of a 21-day cycle until disease progression or unacceptable toxicity.
Coleman noted that response rates were analyzed at different points in the disease course, and also for different patient subgroups based on how many prior lines of therapy had been received.
Of 34 responders in the entire cohort, there were 5 complete responses and 29 partial responses. Duration of response was 6.9 months.
Additionally, 71% of patients experienced tumor reduction and 51% of patients had disease control.
Among patients who had been previously treated for platinum-resistant disease, the ORR was 28.2% vs 34.8% in those who received first-line mirvetuximab for platinum-resistant disease. Of patients who received bevacizumab in the platinum-sensitive setting vs the platinum resistant setting, the ORR was 34% vs 17.6%.
Median overall survival for the entire cohort was 15 months, and this varied by previous therapy; for patients who received one to two lines of prior therapy, median overall survival was 18.7 months compared to 11.6 months for those who had three lines (1 patient had >3 prior lines but was not included in this analysis).
The most common treatment-related adverse events (TRAE; all grade, grade 3-4) included blurred vision (41%, 6%), keratopathy (29%, 9%), and nausea (29%, 0%). TRAEs led to dose delays in 33%, dose reductions in 20%, and discontinuation of therapy in 9% of patients.
Coleman explained that most events were low-grade, reversible ocular and gastrointestinal events that were managed with dose modifications and supportive care.
The study was sponsored by ImmunoGen, manufacturer of mirvetuximab soravtansine. Coleman reports relationships with AbbVie, AstraZeneca, Clovis Oncology, GSK, ImmunoGen, Novocure, OncXerna, Onconova, Eisai, Epsilogen, Pfizer, Merck, Alkermes, Gradalis, Agenus, Mersana, Karyopharm, Deciphera, Roche Genentech, Genelux, Seagen, MerckVBL Therapeutics, and board membership with the GOG Foundation. Mantia-Smaldone reports no relevant financial relationships.
Society of Gynecologic Oncology (SGO) 2023 Annual Meeting on Women’s Cancer. Presented March 25, 2023.
Roxanne Nelson is a registered nurse and an award-winning medical writer who has written for many major news outlets and is a regular contributor to Medscape.
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