In the first randomized, controlled study to explore the efficacy and safety of relacorilant—a selective glucocorticoid receptor modulator—in combination with nab-paclitaxel compared to nab-paclitaxel alone, the combination improved progression-free survival and showed a favorable safety profile in women with recurrent platinum-resistant and/or platinum-refractory ovarian cancer. The findings were presented by Nicoletta Colombo, MD, PhD, and colleagues at the European Society for Medical Oncology (ESMO) Congress 2021 (Abstract 721O).
Preclinical and clinical data indicate that glucocorticoid receptor antagonism may enhance/restore chemotherapy sensitivity.
Nicoletta Colombo, MD, PhD
In their study, the investigators enrolled women with recurrent platinum-resistant or -refractory high-grade serous or endometrioid epithelial ovarian, primary peritoneal, or fallopian tube cancer or ovarian carcinosarcoma with measurable or nonmeasurable disease who had received up to four prior lines of chemotherapy. Patients were randomly assigned 1:1:1 to receive continuous relacorilant daily plus nab-paclitaxel; to receive intermittent relacorilant the day before, of, and after nab-paclitaxel; or to the comparator arm of nab-paclitaxel. A lower dose of nab-paclitaxel was used in combined treatment with relacorilant than in the arm receiving only nab-paclitaxel, because relacorilant inhibits the metabolism of nab-paclitaxel.
The primary endpoint was progression-free survival as determined by the investigators according to Response Evaluation Criteria in Solid Tumors version 1.1. In total, 178 women were randomly assigned: 58 into the continuous relacorilant plus nab-paclitaxel arm, 60 into the intermittent relacorilant plus nab-paclitaxel arm, and 60 into the nab-paclitaxel arm.
Progression-Free Survival
At a median follow-up of 11.07 months, the intermittent regimen significantly improved median progression-free survival compared to nab-paclitaxel alone: 5.55 months vs 3.76 months (hazard ratio [HR] = 0.66, 95% confidence interval [CI] = 0.44–0.98, log-rank test P = .038).
While the objective response rate was similar, duration of response was significantly improved in the intermittent arm vs the nab-paclitaxel alone arm (HR = 0.36, 95% CI = 0.16–0.77, P = .006). Overall survival data were not yet mature for the assessment.
The most common grade ≥ 3 adverse events were neutropenia, anemia, and peripheral sensory neuropathy.
The authors concluded that intermittent relacorilant in combination with nab-paclitaxel improved progression-free survival and showed a favorable safety profile in this population.
Disclosure: The study was funded by Corcept Therapeutics. For full disclosures of the study authors, visit oncologypro.esmo.org.
