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Targeting Ovarian Cancer

Researchers are evaluating the use of folate receptors to treat platinum-resistant ovarian cancer.
BY Kristie L. Kahl
PUBLISHED February 02, 2019
Although the rate at which women are diagnosed with ovarian cancer has decreased bit by bit over the past 20 years, the American Cancer Society estimates that 22,530 women will receive a new diagnosis this year.

To help improve these patients’ outcomes, researchers are evaluating currently available methods as well as emerging treatments.

“There are never enough treatment options out there for patients {with} ovarian cancer. It is a very difficult disease with a very high risk of cancer coming back. Over 80 percent of ovarian cancers will recur, so we need treatment options out there that actually work,” said Floor J. Backes, M.D., assistant professor in the division of gynecologic oncology at The Ohio State University Comprehensive Cancer Center, in an interview with CURE®.

As a frontline, or initial, treatment for ovarian cancer, women typically receive a platinum-based chemotherapy combination regimen, which usually includes cisplatin or carboplatin. When these drugs stop working, the disease is considered platinum resistant. In that circumstance, treatment options include single-agent chemotherapies, such as pegylated liposomal doxorubicin, paclitaxel or topotecan, as well as combination therapies that include the targeted drug Avastin (bevacizumab). Yet more effective, better-tolerated therapies for recurrent ovarian cancer are still needed.

Most recently, researchers have been evaluating the use of folate receptors to target platinum-resistant ovarian cancer. “About 80 percent of high-grade ovarian cancers — the most common type of ovarian cancer — have folate receptor alpha on their cells,” explained Backes. “So, there are some newer drugs called antibody drug conjugates that guide the agents to this receptor. One part of this drug binds to that receptor and has a delivery system to go into the cell so that it is more targeted to just the ovarian cancer cell and hopefully sparing more normal tissue.” The other part of the drug combination is a chemotherapy that, due to this delivery system, is able to attack the cancer cells from within.

Because these drugs are designed to specifically attack cancer cells and not healthy tissues, they are less likely to cause side effects such as hair loss and neuropathy (nerve damage) than regimens consisting strictly of chemotherapy. Drugs in this class include the experimental mirvetuximab soravtansine (IMGN853).

As of yet, there are no drugs that target folate receptors approved by the Food and Drug Administration (FDA). However, the agency did grant a fast-track designation to mirvetuximab soravtansine for the treatment of patients whose platinum-resistant ovarian cancers express medium to high levels of folate receptor alpha; who received at least one, but no more than three, prior systemic treatment regimens (which treat cancer by spreading throughout the body); and for whom treatment with one chemotherapy is appropriate as the next line of therapy. Under a fast-track designation, the FDA gives an expedited review to a drug that might fill an unmet medical need.

The drug is being evaluated in the phase 3 FORWARD I trial, designed to test mirvetuximab soravtansine compared with the physician’s choice of single-agent chemotherapy in 333 patients with platinum-resistant ovarian cancer that expresses medium or high levels of folate receptor alpha who have been treated with up to three prior regimens. Progression-free survival — or the length of time during and after treatment that a patient lives with the disease without it getting worse — is the primary endpoint of the study.

In addition, the agent is being assessed as part of multiple drug combinations in the phase 1b/2 FORWARD II trial. That trial is designed to evaluate mirvetuximab soravtansine in combination with Avastin or the immunotherapy Keytruda (pembrolizumab) in patients with folate receptor alpha-positive, platinum-resistant ovarian cancer, primary peritoneal cancer or fallopian tube tumors. It will also test a triple combination of mirvetuximab soravtansine plus carboplatin and Avastin in patients with platinum-sensitive ovarian cancer.

While folate receptors are being tested for the treatment of women with platinum-resistant ovarian cancer, Backes urged individuals to get involved in clinical studies.

“Currently, (these agents) are still in clinical trials, so it is a very exciting option, but we are still studying it,” Backes said. “Patients should participate in the clinical trials so that researchers can complete them, and hopefully those drugs will become available on the market for everybody.”

This content is sponsored by ImmunoGen.
 
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