Relacorilant regimen prolongs survival in recurrent platinum-resistant ovarian cancer
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CHICAGO — Intermittent relacorilant plus nab-paclitaxel demonstrated an OS benefit among women with recurrent platinum-resistant/refractory ovarian cancer compared with nab-paclitaxel alone.
Researchers observed greater OS improvement among women without primary platinum-refractory disease, results presented at ASCO Annual Meeting showed.
Rationale and methods
“There remains a large unmet need for effective and well-tolerated treatments for women with platinum-resistant ovarian cancer,” Nicoletta Colombo, MD, PhD, associate professor of obstetrics and gynecology at University of Milan-Bicocca in Milan, said during her presentation. “Single-agent chemotherapies are commonly used in this setting, but outcomes are generally poor. Cortisol has been shown to contribute to chemotherapy resistance by suppressing apoptic pathways that cytotoxic agents, such as nab-paclitaxel, utilize.”
Previous findings from a three-arm, randomized, open-label, phase 2 study showed improved PFS and a favorable safety profile with the selective glucocorticoid receptor modulator relacorilant (Corcept Therapeutics) plus nab-paclitaxel (Abraxane, Bristol Myers Squibb) among patients with recurrent platinum-resistant/refractory ovarian cancer who received up to four prior lines of chemotherapy.
For the current analysis, researchers assigned 178 women (median age, 61 years; 36.5% platinum-refractory) 1:1:1 to nab-paclitaxel dosed at 80 mg/m² plus intermittent relacorilant dosed at 150 mg once-daily the day before, of and after nab-paclitaxel (n = 60); nab-paclitaxel dosed at 80 mg/m² plus continuous relacorilant dosed at 100 mg once-daily (n = 58); or 100 mg/m² nab-paclitaxel alone (n = 60). Nab-paclitaxel was administered on days 1, 8 and 15 of every 28-day cycle.
Colombo presented results of the secondary endpoint of OS.
Key findings
Results of the predefined OS analysis that included 128 events showed HRs of 0.67 (95% CI, 0.43-1.03) with intermittent and continuous relacorilant vs. 0.85 (95% CI, 0.56-1.29) with nab-paclitaxel alone.
Median OS was 13.9 months (95% CI, 11.1-18.4) in the intermittent relacorilant group, 11.3 months (95% CI, 7.5-16.4) in the continuous relacorilant group and 12.2 months (95% CI, 7.7-15.3) in the nab-paclitaxel-alone group.
Researchers additionally observed a statistically significant improvement in OS (HR = 0.63; 95% CI, 0.39-0.99) among a subgroup of women without primary platinum-refractory disease.
“As of March 7, 2022, it was reassuring to see that, especially for the intermittent group, the addition of relacorilant to nab-paclitaxel did not result in any additional safety events,” Colombo said. “Safety and tolerability were comparable, with neutropenia as the most common grade 3 or higher adverse event reported. Of note, no febrile neutropenia events were observed in those treated with relacorilant. All patients treated with relacorilant received one dose of prophylactic growth factor to reduce the risk of neutropenia.”
Looking ahead
Researchers have initiated a phase 3 trial examining intermittent relacorilant plus nab-paclitaxel compared with investigator’s choice of chemotherapy among patients without primary platinum-refractory disease.
“The upcoming phase 3 trial plans to enroll about 360 patients with platinum-resistant or platinum-refractory high serous endometrioid epithelial ovarian cancer who received up to three prior lines of therapy, and patients with primary platinum-refractory disease will be excluded,” Colombo said.
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Colombo N, et al. Abstract LBA5503. Presented at: ASCO Annual Meeting; June 3-7, 2022; Chicago.
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