麻豆传媒

CHICAGO -- An antibody-microtubule inhibitor conjugate improved survival in selected patients with advanced platinum-resistant ovarian cancer compared with standard chemotherapy, representing the first novel drug to do so in a phase III trial for this difficult-to-treat population.

Women in the trial treated with the recently approved drug, mirvetuximab soravtansine (Elahere), experienced a significant 1.6-month improvement in progression-free survival (PFS) and a nearly 4-month gain in median overall survival (OS) versus those assigned to physician's choice of chemotherapy, reported Kathleen N. Moore, MD, of the Stephenson Cancer Center at the University of Oklahoma in Oklahoma City.

The results will be "practice changing," she said during a press conference here at the American Society of Clinical Oncology (ASCO) annual meeting.

"There has never been a presentation or a clinical trial of a novel agent in the platinum-resistant space that has demonstrated improvement in overall survival, until now," said Moore, noting that bevacizumab's 2014 approval in this setting was based on a PFS benefit alone.

The so-called included 453 women with platinum-resistant, advanced high-grade epithelial ovarian, primary peritoneal, or fallopian tube cancers and high folate receptor α (FRα) expression. While most high-grade serous ovarian cancers express FRα, about 35-40% of tumors have high levels of expression, she said.

Response to treatment was significantly greater with mirvetuximab soravtansine (42%, including 12 complete responses) versus chemotherapy (12%, no complete responses, P<0.0001), and the survival improvement was similar regardless of prior bevacizumab exposure, Moore reported.

"This is really important for our patients," said ASCO-designated expert Merry Jennifer Markham, MD, of the University of Florida in Gainesville. "The MIRASOL study is practice changing for this population of women who have platinum-resistant ovarian cancer and this folate receptor α high expression."

She explained that over time, women with platinum-resistant ovarian or fallopian tube cancers are typically resistant to other chemotherapy options as well.

"These women ultimately may need their standard chemotherapy, but this allows the delay and postponing of those toxic treatments that we know have a very poor survival curve," said Markham. "Women are happy to delay toxic chemotherapy when they're dealing with this diagnosis."

She added that until now, the best recommendation for subsequent treatment in this population has been enrollment in a clinical trial. "These women have been waiting a long time for progress, and I think this MIRASOL study is progress."

Moore noted that the drug has also shown activity in patients with lower levels of FRα expression as well.

To be eligible for the study, women had to have been diagnosed with high-grade serous, platinum-resistant disease, and have FRα detected in at least 75% of tumor cells. Patients were also required to have undergone one to three previous lines of therapy, with prior exposure to bevacizumab and PARP inhibitor therapy allowed. BRCA-positive patients were eligible to enroll as well, Moore said.

Women in the study were about age 53 years and roughly 60% were diagnosed with stage III cancer at their initial diagnosis. Nearly all had previously been treated with taxanes, approximately 60% had a history of bevacizumab therapy, and about 55% had been treated with PARP inhibitors.

Eligible patients were randomized 1:1 to either mirvetuximab soravtansine (6 mg/kg every 3 weeks) or investigator's choice of chemotherapy -- paclitaxel, pegylated liposomal doxorubicin, or topotecan. Patients were stratified by the type of chemotherapy and by number of lines of previous chemotherapy.

In the full study population, the median PFS was 5.62 months in the mirvetuximab soravtansine arm compared with 3.98 months in the chemotherapy arm, representing a 35% reduction in the risk for disease progression or death (HR 0.65, 95% CI 0.52-0.81, P<0.0001).

OS reached 16.46 months with the study drug versus 12.75 months with chemotherapy, a 33% reduction in the risk for death over the course of the trial (HR 0.67, 95% CI 0.50-0.89, P=0.0046).

In women who had received bevacizumab, the PFS was 36% higher in the mirvetuximab soravtansine arm, while OS was 26% higher. For those who had not, PFS was 34% higher and OS was 49% higher with the antibody-microtubule inhibitor conjugate.

The safety profile of mirvetuximab soravtansine was generally consistent with prior reports, with adverse events (AEs) predominantly consisting of low-grade gastrointestinal and ocular toxicity, including blurred vision (41%), keratopathy (32%), and dry eye (28%).

Grade ≥3 AEs were less frequent with mirvetuximab soravtansine (42% vs 54% with standard chemotherapy) as were serious AEs (24% vs 33%). While more patients on mirvetuximab soravtansine had dose reductions for AEs (34% vs 24%), fewer discontinued treatment for toxicity (9% vs 16%).

"It's so well tolerated, the hematologic toxicity is nil, and it works," said Moore.

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