Intermittent relacorilant + nab-paclitaxel improves survival outcomes and response duration in platinum-resistant/refractory ovarian cancer compared to nab-paclitaxel monotherapy, according to the results of a phase II study.
Treatment of advanced epithelial ovarian cancer is challenging. Most patients who initially respond to platinum-based chemotherapy eventually develop resistance. Patient outcomes are poor in platinum-resistant/refractory ovarian cancer treated with sequential single-agent chemotherapy. Relacorilant may restore chemosensitivity through selective glucocorticoid receptor modulation.
A three-arm, randomized, controlled, open-label phase II study evaluated the efficacy and safety of relacorilant + nab-paclitaxel in platinum-resistant/refractory ovarian cancer compared with nab-paclitaxel monotherapy. The study’s results were published in the Journal of Clinical Oncology.
Study Population
A total of 178 patients were enrolled. The median age was 61 years. Out of 178, 177 patients had received prior taxane. The proportion of platinum-refractory patients was 36.5%. Patients were randomized to intermittent relacorilant (150 mg) + nab-paclitaxel (80 mg/m2), continuous relacorilant (100 mg) + nab-paclitaxel (80 mg/m2), or nab-paclitaxel monotherapy (100 mg/m2).
Intermittent Relacorilant + Nab-Paclitaxel Improves Survival Rates
At the primary analysis (median follow-up: 11.1 months), treatment with intermittent relacorilant led to greater improvement in progression-free survival (PFS) than nab-paclitaxel monotherapy (hazard ratio (HR): 0.66, P=0.038), with a median PFS of 5.6 vs. 3.8 months. The median PFS was 5.3 months in the continuous arm (HR: 0.83, P=0.329). After multiplicity adjustment, the primary endpoint (simultaneous testing of both relacorilant-treated arms vs. nab-paclitaxel monotherapy) did not reach statistical significance (P<0.025).
At the predefined overall survival (OS) analysis (median follow-up: 22.5 months), HRs were 0.67 (P=0.066) and 0.85 (P=0.447) for the intermittent and continuous relacorilant versus nab-paclitaxel monotherapy arms, respectively. The median OS was 13.9, 11.3, and 12.2 months in the intermittent, continuous, and nab-paclitaxel monotherapy arms, respectively. An ad-hoc analysis demonstrated consistent PFS and OS benefit across subgroups in the intermittent arm versus nab-paclitaxel monotherapy, with greater improvement in OS in patients who received one to three prior lines of therapy (including bevacizumab and excluding those with primary platinum-refractory disease).
Intermittent Relacorilant Regimen Significantly Prolongs DOR Compared to Nab-Paclitaxel Monotherapy
Although the objective response rates were similar across study arms, the duration of response (DOR) was significantly prolonged in the intermittent relacorilant arm than in the nab-paclitaxel monotherapy arm. CA-125 responses per the Gynecological Cancer InterGroup criteria were observed in 64.2%, 62.7%, and 53.8% of patients in the intermittent, continuous, and nab-paclitaxel monotherapy arms, respectively.
Intermittent Relacorilant Regimen Demonstrates a Favorable Safety Profile
Adverse events (AEs) were similar across all study arms. Overall, intermittent relacorilant + nab-paclitaxel was tolerated better than the continuous relacorilant regimen. Higher grade≥3 fatigue was seen in both relacorilant arms compared to nab-paclitaxel monotherapy, whereas other grade ≥3 AEs (i.e., neutropenia, peripheral neuropathy) were lower in the intermittent arm versus nab-paclitaxel monotherapy.
All relacorilant-treated patients and 46.7% of patients on nab-paclitaxel monotherapy received growth-colony stimulating factor. The most common AEs were fatigue, nausea, anemia, abdominal discomfort, peripheral neuropathy, constipation, alopecia, neutropenia, and vomiting. Rash occurred with higher frequency in the continuous arm, with one grade ≥3 event. Serious AEs occurred in 26.7%, 54.4%, and 31.7% of patients in the intermittent, continuous, and nab-paclitaxel monotherapy arms, respectively. Three AEs resulted in death; however, none were related to the study drug.
Source
Colombo, N., Van Gorp, T., Matulonis, U. A., Oaknin, A., Grisham, R. N., Fleming, G. F., Olawaiye, A., Nguyen, D. D., Greenstein, A. E., Custodio, J. M., Pashova, H. I., Tudor, I. C., & Lorusso, D. (2023). Relacorilant + NAb-Paclitaxel in patients with recurrent, Platinum-Resistant ovarian Cancer: a Three-Arm, randomized, controlled, Open-Label Phase II study. Journal of Clinical Oncology, 41(30), 4779–4789. https://doi.org/10.1200/jco.22.02624
