AN INVESTIGATIONAL DRUG that blocks the effects of cortisol to improve chemotherapy responses extended survival in women with platinum-resistant ovarian cancer. Adding relacorilant, a glucocorticoid receptor antagonist, to weekly nab-paclitaxel chemotherapy treatment, led to more women with ovarian cancer living longer without their disease progressing—a measure known as progression-free survival—and improved overall survival, according to the interim results published June 21 in the Lancet.

In the phase III randomized trial, 381 women with ovarian, primary peritoneal or fallopian tube cancer were randomly assigned to receive relacorilant and nab-paclitaxel (188 patients) or nab-paclitaxel alone (193 patients). The trial was open label, meaning there was no placebo and the participants were informed what treatments they were given. Everyone in the trial had platinum-resistant cancer—cancer that initially responded to treatment with drugs that contain the metal platinum, such as cisplatin and carboplatin, then recurred within six months. Nab-paclitaxel is a taxane, which is a chemotherapy that disrupts cell growth by preventing cell division, and is formulated with a protein called albumin, which enhances chemotherapy delivery into cancer cells.

Patients in the relacorilant/nab-paclitaxel group received relacorilant in pill form the day before, the day of and the day after IV infusions with nab-paclitaxel. Treatment continued until the disease progressed or treatment side effects became intolerable. Participants in both groups had previously received one to three lines of chemotherapy and bevacizumab, a monoclonal antibody medication designed to slow tumor growth.

Improving Chemotherapy Sensitivity

In the trial, the relacorilant and nab-paclitaxel combination resulted in a modest improvement in median progression-free survival, or the median length of time patients live without their disease worsening. The progression-free survival was 6.54 months for the group receiving relacorilant versus 5.52 months for the group given nab-paclitaxel alone. Those given relacorilant also had a nearly five-month increase in median overall survival (15.97 months versus 11.5 months), compared with nab-paclitaxel alone. “Adding relacorilant, which blocks the glucocorticoid receptor at the cellular level, improves chemotherapy sensitivity,” says David M. O’Malley, a co-author of the study and a gynecologic oncologist at Ohio State University Comprehensive Cancer Center in Columbus. “From previous trials, we know high cortisol levels are a negative diagnostic indicator in patients with ovarian cancer.”

Although the trial is not yet completed, O’Malley says he expects the final analysis will continue to show a sustained increase in both progression-free and overall survival rates in patients with platinum-resistant ovarian cancer receiving the combination. “In the context of real numbers, it’s a 30% improvement in progression-free survival and a 31% overall survival improvement,” he says. “We’re seeing people with sustained improvement in their disease, which will change the landscape of how we approach patients with platinum-resistant ovarian cancer.” Although more treatments are being investigated, patients have traditionally had limited options. The outcome for patients with platinum-resistant ovarian cancer remains generally poor, with median survival of less than a year.

Based on the trial’s interim results, relacorilant has been submitted to the Food and Drug Administration (FDA). If approved, relacorilant could become another treatment option for people with platinum-resistant disease. “We haven’t seen an overall survival benefit in the platinum-resistant ovarian cancer setting, so this really exciting,” says Shannon Westin, a gynecologic oncologist at the University of Texas MD Anderson Cancer Center in Houston, who was not part of the study.

Moreover, “in this era of precision medicine, the combination seemed to work for people with platinum-resistant ovarian cancer who don’t have biomarkers that have other drugs available,” Westin says. Adding relacorilant to treatment did not lead to an increase in side effects, but she notes that weekly taxane chemotherapy can be challenging. Side effects can include hair loss, neuropathy, fatigue, nausea and diarrhea, plus the logistics of attending weekly treatments.

Relacorilant is currently available only in clinical trials, so O’Malley recommends that patients diagnosed with platinum-resistant ovarian cancer talk to their doctor about their treatment options. Though there are multiple chemotherapies available for this group, he says a weekly taxane, such as nab-paclitaxel, has been found more effective in most patients. For platinum-resistant ovarian cancer, he says “taxane chemotherapy alone has about a 30% response rate, outperforming other, non-taxane agents.”

Sandra Gordon is a medical writer in Stamford, Connecticut.