The conclusion of this study marks the first time that a novel therapy has demonstrated an overall survival (OS) improvement in any phase 3 trial in this population, according to lead investigator Kathleen Moore, MD.
“We believe these data are practice changing and position mirvetuximab [soravtansine] as the new standard of care for patients with folate receptor–alpha positive, platinum-resistant ovarian cancer,” said Dr. Moore during a presentation of the study at a special session of the annual meeting of the American Society of Clinical Oncology devoted solely to the MIRASOL study.
New standard of care
Following Dr. Moore’s presentation, Roisin Eilish O’Cearbhaill, MD, served as a discussant, and she confirmed the trial’s importance.
“It has firmly established the role of mirvetuximab [soravtansine] in folate receptor–alpha high-expression, platinum-resistant ovarian cancer,” said Dr. O’Cearbhaill, who is Research director of the gynecologic medical oncology service and clinical director of the solid tumor, cellular therapy service at Memorial Sloan Kettering Cancer Center, New York.
Mirvetuximab soravtansine received accelerated FDA approval in November based on the results of the single-arm SORAYA trial, which demonstrated a progression-free survival (PFS) benefit in platinum-resistant patients who had been previously treated with one to three treatment regimens, at least one of which having included bevacizumab.
The new study compared MIRV with physician choice chemotherapy and found both a PFS and OS benefit in the MIRV arm. The results garnered significant enthusiasm from the audience, and others reacted positively as well.
“The results that she presented are just astounding, with a significant improvement in both progression-free and overall survival. I think certainly the overall survival needs to be highlighted here, because this is a patient population that’s notoriously difficult to treat,” said Ana Valente, MD, a gynecologic oncologist at the Ochsner Health System in New Orleans. Dr. Valente, who did not attend the presentation but was asked to comment on the study, is also a member of the Society of Gynecological Oncologist communications committee.
Unlike SORAYA, MIRASOL was open to patients who had not received bevacizumab, and Dr. Moore and colleagues found similar survival benefits in patients who had not received bevacizumab as in those who had, said Dr. Moore, who is the associate director of clinical research at Stephenson Cancer Center and director of the Oklahoma TSET Phase 1 Program, both in Oklahoma City. This opens the possibility of using MIRV instead of bevacizumab combined with chemotherapy in platinum-resistant patients.
“I think this data really shows you can move right to mirvetuximab [soravtansine] and feel pretty solid about the decision in a biomarker selected [population],” Dr. Moore said, during an interview.
Not just for high expression levels
MIRASOL was restricted to patients with high levels of expression of folate receptor–alpha, which is MIRV’s target on the surface of tumor cells. High expression is defined as at least 75% of viable tumor cells exhibiting a minimum of 2+ level membrane staining intensity by immunohistochemistry. That represents about 35% of patients, according to Dr. Moore, but she said that the drug also shows promise in patients with medium levels of folate receptor–alpha expression.
“I think it’s just going to be now starting to get those label extension studies launched to branch it out. Then you account for 60% of your population which [have] medium to high [expression levels], and that’s really where you see benefit,” said Dr. Moore. Medium expression levels of folate receptor–alpha are defined as 50% to greater than 75% of tumor cells with 2+ level membrane staining intensity.
She also noted that the FORWARD II trial combining mirvetuximab soravtansine with bevacizumab in platinum-resistant ovarian cancer is showing good results.
“We have really beautiful data [from FORWARD II]. If I have a medium expresser, I’m using the doublet [of MIRV and bevacizumab], and it works,” said Dr. Moore, while also pointing out that this remains an off-label use.
It’s possible that the drug could be extended even to low expression levels, defined as 25% to less than 50% of tumor cells with 2+ level membrane staining intensity. “[We are] currently working on that strategy with already available data,” said Dr. Moore.
She speculated that the improved OS may be attributed to the reduced toxicity of MIRV, compared with chemotherapy agents, which leaves patients feeling better and more able to pursue other treatments, which in turn may increase survival odds.
Dr. O’Cearbhaill touted the benefits of ADCs and their ability to target powerful cytotoxic agents while limiting side effects, and she is looking forward to more new therapies on the horizon.
“There are four [ADCs] in late stages of development [for platinum-resistant ovarian cancer], so hopefully there will be other ones coming online as well,” Dr. O’Cearbhaill said in an interview. “Then we’ll have to figure out how to sequence them, which drug will be best in class. Will we be just giving one or will be giving ADC followed by ADC?”
Study methods and results
The study enrolled 453 patients and randomized them to treatment with MIRV or investigator’s choice of chemotherapy, which could be paclitaxel, pegylated liposomal doxorubicin, or topotecan. The MIRV dose was 6 mg/kg adjusted ideal body weight every 3 weeks. The median age was 62 in the chemotherapy arm and 63 years in the MIRV arm. About 63% of the chemotherapy arm had prior bevacizumab exposure, as did 61% of the MIRV arm.
Median PFS was 5.62 months in the MIRV arm and 3.98 months in the chemotherapy arm (hazard ratio, 0.65; P less than .0001). The overall response rate was 42% in the MIRV arm and 16% in the chemotherapy arm (P < .0001).
The safety outcomes also favored MIRV: 42% experienced grade 3 or higher treatment-emergent adverse events (TEAEs) versus 54% in the chemotherapy group. Severe adverse events were also lower in MIRV, 24% versus 33%. Just 9% of patients in the MIRV discontinued because of TEAEs, compared with 16% in the chemotherapy arm.
MIRV was associated with blurred vision (41%), keratopathy (32%), and dry eye (28%), but these issues were generally manageable through collaboration with optometrists or ophthalmologists.
Dr. Moore and Dr. O’Cearbhaill reported receiving honoraria, research funding, and travel expenses from numerous pharmaceutical companies. Dr. O’Cearbhaill has consulted for or advised Aptitude Health, Bayer, Carina Biotech, Fresenius Kabi, GlaxoSmithKline, GOG Foundation, Immunogen, R-Pharm, Regeneron, and Seagen.