Overall survival (OS) data from a phase 2 clinical trial confirm the benefit of intermittent relacorilant plus nab-paclitaxel versus nab-paclitaxel alone for patients with ovarian cancer, especially those without primary platinum refractory disease. These data were presented at the 2022 ASCO Annual Meeting by Nicoletta Colombo, MD, University of Milan-Bicocca, European Institute of Oncology, Italy, and colleagues.

“Cortisol contributes to chemotherapy resistance by suppressing apoptotic pathways that cytotoxic agents utilize. Preclinical and clinical data indicate that glucocorticoid receptor modulation with relacorilant reverses the anti-apoptotic effects of cortisol and restores the efficacy of cytotoxic agents,” wrote Dr Colombo et al.

“We report OS results from a randomized, controlled phase 2 study of relacorilant plus nab-paclitaxel compared to nab-paclitaxel only in patients with ovarian cancer,” wrote Dr Colombo et al, who conducted the open-label, 3-arm study comprising 178 women with recurrent, platinum-resistant/refractory, high-grade serous or endometrioid epithelial ovarian, primary peritoneal, or fallopian tube cancer, or ovarian carcinosarcoma previously treated with ≤4 chemotherapies.

All patients were randomized in a 1:1:1 ratio to receive nab-paclitaxel 80 mg/m2 plus intermittent relacorilant 150 mg once daily the day before, of, and after nab-paclitaxel (n = 60); nab-paclitaxel 80 mg/m2 plus continuous relacorilant 100 mg once daily (n = 58); or c) nab-paclitaxel only 100 mg/m2 (n = 60).

Patients were given nab-paclitaxel on days 1, 8, and 15 of each 28-day cycle. The primary and secondary end points were PFS and OS, respectively. Dr Colombo and co-investigators used a 2-sided log-rank test at a 0.05 level of significance without multiplicity adjustment to compare OS data for the intermittent and continuous arms.

By the point at which 128 OS events had been reported (a predefined cutoff for OS analysis), hazard ratios (HRs) for intermittent and continuous relacorilant plus nab-paclitaxel vs nab-paclitaxel-only arms were 0.67 (95% confidence interval [CI], 0.43 to 1.03; P = .066) and 0.85 (95% CI, 0.56 to 1.29; P = .447), respectively.

Among patients in the intermittent relacorilant plus nab-paclitaxel, continuous relacorilant plus nab-paclitaxel, and nab-paclitaxel-only arms, the median OS was 13.9 (95% CI, 11.1 to 18.4), 11.3 (95% CI, 7.5 to 16.4), and 12.2 (95% CI, 7.7 to 15.3) months, respectively. The investigators observed a statistically significant improvement in OS among patients without primary platinum-refractory disease, with a HR of 0.63 (95% CI, 0.39 to 0.99; P = .045) and median OS of 13.9 (95% CI, 11.1 to 18.4) vs 12.2 (95% CI, 7.7 to 15.3) months for intermittent relacorilant plus nab-paclitaxel versus nab-paclitaxel-only arms.

“In addition to the improved PFS and duration of response observed at the primary analysis, the OS analysis confirmed the survival benefit of intermittent relacorilant plus nab-paclitaxel compared to nab-paclitaxel only, particularly in patients who were not primary platinum refractory,” the investigators reported.

“A phase 3 trial evaluating intermittent relacorilant plus nab-paclitaxel versus investigator’s choice of chemotherapy in patients without primary platinum-refractory disease is ongoing (NCT05257408),” they concluded.

Source:

Colombo N, Van Gorp T, Matulonis UA, et al. Overall survival data from a 3-arm, randomized, open-label, phase 2 study of relacorilant, a selective glucocorticoid receptor modulator, combined with nab-paclitaxel in patients with recurrent platinum-resistant ovarian cancer. Presented at: ASCO Annual Meeting; June 3-7, 2022; Chicago, IL; and virtual. Abstract LBA5503.