In a phase II trial reported in the Journal of Clinical Oncology, Nicoletta Colombo, MD, and colleagues found that the selective glucocorticoid receptor modulator relacorilant (given on an intermittent schedule) plus nab-paclitaxel showed benefits vs nab-paclitaxel alone in patients with recurrent, platinum-resistant ovarian cancer.
As stated by the investigators, “Despite therapeutic advances, outcomes for patients with platinum-resistant/refractory ovarian cancer remain poor. Selective glucocorticoid receptor modulation with relacorilant may restore chemosensitivity and enhance chemotherapy efficacy.”
Nicoletta Colombo, MD
Study Details
In the open-label trial, 178 patients from sites in North America and Europe were randomly assigned 1:1:1 between April 2019 and July 2020 to receive nab-paclitaxel at 80 mg/m2 plus intermittent relacorilant at 150 mg the day before, of, and after nab-paclitaxel (n = 60); nab-paclitaxel at 80 mg/m2 plus continuous relacorilant at 100 mg once daily (n = 58); or nab-paclitaxel at 100 mg/m2 (n = 60). Nab-paclitaxel was given on days 1, 8, and 15 of each 28-day cycle. The primary endpoint was investigator-assessed progression-free survival.
Progression-Free Survival
Median follow-up for progression-free survival at primary analysis was 11.1 months. Median progression-free survival was 5.6 months in the intermittent relacorilant group vs 3.8 months in the nab-paclitaxel group (hazard ratio [HR] = 0.66, 95% confidence interval [CI] = 0.44–0.98, P = .038); the difference did not meet the significance level of P < .025 for multiplicity adjustment. Median progression-free survival in the continuous relacorilant group was 5.3 months (HR vs nab-paclitaxel group = 0.83, 95% CI = 0.56–1.22, P = .329).
Objective response rates across groups were 35.7%, 35.2%, and 35.8%. Median duration of response was better in the intermittent relacorilant group vs the nab-paclitaxel group (5.55 vs 3.65 months, HR = 0.36, P = .006), with no difference observed between the continuous relacorilant group (3.79 months, HR = 0.72, P = .423) vs the nab-paclitaxel group.
At a preplanned overall survival analysis at a median follow-up of 22.5 months, median overall survival was 13.9 months in the intermittent relacorilant group (HR vs nab-paclitaxel group = 0.67, P = .066), 11.3 months in the continuous relacorilant group (HR = 0.85, P = .447), and 12.2 months in the nab-paclitaxel group.
KEY POINTS
- Benefits were observed with the addition of intermittent relacorilant to nab-paclitaxel.
- Less benefit was observed with the addition of continuous relacorilant to nab-paclitaxel.
Adverse Events
The most common grade ≥ 3 adverse events across the intermittent relacorilant, continuous relacorilant, and nab-paclitaxel groups were neutropenia (in 6.7%, 26.3%, and 15.0% of patients, respectively), anemia (13.3%, 19.3%, 11.7%), peripheral neuropathy (0%, 15.8%, 5.0%), and fatigue/asthenia (11.7%, 8.8%, 1.7%). Serious adverse events occurred in 26.7%, 54.4%, and 31.7% of patients. No treatment-related deaths were observed.
The investigators concluded, “Intermittent relacorilant [plus] nab-paclitaxel improved progression-free survival, duration of response, and overall survival compared with nab-paclitaxel monotherapy. On the basis of protocol-prespecified… multiplicity adjustment, the primary endpoint did not reach statistical significance (P < .025). A phase III evaluation of this regimen is underway (ClinicalTrials.gov identifier NCT05257408).”
Dr. Colombo, of the European Institute of Oncology, IRCCS, University of Milan-Bicocca, Milan, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Corcept Therapeutics Inc. For full disclosures of the study authors, visit ascopubs.org.
