In the first randomised, 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, combined treatment improved progression-free survival (PFS) and showed a favourable safety profile among the women with recurrent platinum-resistant and/or platinum-refractory ovarian cancer. The findings are presented by Dr. Domenica Lorusso of the Gynaecology Oncology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS in Rome, Italy during the proffered papers session on gynaecological cancers at ESMO Congress 2021 (16-21 September).
Dr. Lorusso told the audience that preclinical and clinical data indicate that glucocorticoid receptor antagonism may enhance/restore chemotherapy sensitivity. In their study, the investigators randomised women with recurrent platinum-resistant or refractory high-grade serous or endometroid epithelial ovarian, primary peritoneal, or fallopian tube cancer or ovarian carcinosarcoma with measurable or non-measurable disease and who received up to 4 prior chemotherapy lines in 1:1:1 mode to receive continuous relacorilant daily plus nab-paclitaxel, or intermittent relacorilant the day before, of, and after nab-paclitaxel, or comparator arm of nab-paclitaxel.
Lower dose of nab-paclitaxel was used in combined treatment with relacorilant than in a single arm nab-paclitaxel, because relacorilant inhibits the metabolism of nab-paclitaxel. The study primary endpoint was PFS determined by the investigators according RECIST v1.1.
In total, 178 women were randomised, 58 in the continuous relacorilant plus nab-paclitaxel arm, 60 in the intermittent relacorilant plus nab-paclitaxel arm, and 60 in the nab-paclitaxel arm. At median follow-up of 11.07 months, the intermittent regimen significantly improved median PFS compared to nab-paclitaxel alone, 5.55 versus 3.76 months (hazard ratio [HR] 0.66, 95% confidence interval [CI] 0.44-0.98; log-rank test p = 0.038).
While objective response rate was similar, duration of response was significantly improved in the intermittent arm versus nab-paclitaxel alone arm (HR 0.36, 95% CI 0.16-0.77; p = 0.006).
Overall survival is not mature yet for the assessment.
Most common grade ≥3 adverse events were neutropenia, anaemia, and peripheral sensory neuropathy.
The authors concluded that intermittent relacorilant in combination with nab-paclitaxel improved PFS and showed a favourable safety profile in this population.
The study was funded by Corcept Therapeutics.
721O – Colombo N, Nguyen DD, Fleming GF, et al. Relacorilant, a selective glucocorticoid receptor modulator, in combination with nab-paclitaxel improves progression-free survival in patients with recurrent platinum-resistant ovarian cancer: A 3-arm, randomized, open-label, phase II study. ESMO Congress 2021 (16-21 September).