MIRASOL, an international phase III randomised clinical trial, found that mirvetuximab soravtansine, an antibody and microtubule inhibitor conjugate, significantly improved progression-free and overall survival for women with platinum-resistant, advanced high-grade epithelial ovarian, primary peritoneal, or fallopian tube cancers with high folate receptor-alpha expression.

The research was presented at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting.

Women who received mirvetuximab soravtansiine not only lived longer when considering all standard chemotherapy medicines together but also each individual drug by itself in this trial.

Survival outcomes with mirvetuximab soravtansine were also better, regardless of whether a person received bevacizumab prior to mirvetuximab soravtansine compared to the use of a physician’s choice of chemotherapy.

With a median follow-up of 13.1 months, in the group of 281 women that had previously been treated with bevacizumab, PFS was 36% better and OS was 26% better for women who received mirvetuximab soravtansine vs. the physician’s choice of standard chemotherapy.

In the group of 172 women that had not previously received bevacizumab, PFS was 34% better and OS was 49% better for women who received mirvetuximab soravtansine vs. the physician’s choice of standard chemotherapy.

The adverse event profile of mirvetuximab soravtansine was consistent with prior reports -- predominantly low-grade ocular and gastrointestinal events. For women taking mirvetuximab soravtansine, 14% remained on the study drug vs. 3% of women receiving physician’s choice of standard chemotherapy.

“Mirvetuximab soravtansine has fewer serious side effects, especially those that can lead to stopping treatment, compared to standard chemotherapies for patients with platinum-resistant ovarian cancer. This, coupled with the overall survival advantage, demonstrates progress and offers hope for these patients,” said Merry Jennifer Markham, MD, FACP, FASCO, ASCO Expert.

“Mirvetuximab soravtansine has an FDA accelerated approval so it is hoped that this trial result leads to a quick formal approval.  But more importantly, it opens the door globally for the drug to be available outside the U.S. where accelerated approval isn't an option. It’s also worth noting that ongoing studies are evaluating moving the drug to being used in earlier stages of the disease,” said Kathleen N. Moore, MD, MS, associate director of clinical research and co-director of the Cancer Therapeutics Program at the Stephenson Cancer Center at the University of Oklahoma in Oklahoma City, OK.

Single-agent chemotherapies have shown limited activity and considerable toxicity in patients with platinum-resistant epithelial ovarian cancer.

Each successive line of therapy is associated with progressively lower response rates and many patients have difficulty tolerating additional treatments.

There have been no new agents specifically indicated for the disease since 2014 when bevacizumab was approved for use with chemotherapy.

The investigational drug used in this trial, mirvetuximab soravtansine, demonstrated clinically meaningful antitumor activity in the single arm SORAYA trial reported in January 2023. 

This trial is a confirmatory phase III study to test the efficacy of the drug in this setting.

Mirvetuximab soravtansine targets folate receptor-alpha, which is a member of the folate receptor family that is overexpressed on a variety of epithelial-derived cancer cells. When the drug binds to the receptor, it becomes internalised and leads to cell death.

In 2023, there will be an estimated 19,710 new cases and 13,270 deaths in the U.S due to ovarian cancer.

If the cancer spreads to distant sites, as is the case with women in this trial, the five-year survival rate is 30%.

Over 70% of people annually are diagnosed at this advanced stage.

Mirvetuximab soravtansine has now been shown to be most effective when expression of folate receptor-alpha is high. But the investigators found some efficacy when expression levels were moderate or low, which is something they hope to examine more definitively in future studies. 

They also hope to incorporate the drug into earlier lines of therapy, including platinum-sensitive, recurrent disease.

Source: ASCO