Ovarian cancer ranks fifth in cancer deaths among women, accounting for more deaths than any other cancer of the female reproductive system [20]. A woman's risk of getting ovarian cancer is about 1 in 78. Typically, treatment plans are based on the type and stage of ovarian cancer.
With systemic treatment, chemotherapy resistance is a major concern in advanced platinum-resistant and platinum-refractory ovarian cancer. One mechanism of resistance is driven by cortisol, which can suppress the apoptotic pathways that chemotherapy agents require. Relacorilant is a selective glucocorticoid receptor modulator that has shown promise in overcoming resistance when combined with taxanes. ROSELLA is a Phase 3, randomized, two-arm, open-label, multicenter study of relacorilant and nab-paclitaxel compared to the investigator’s choice of chemotherapy agents in patients with confirmed high-grade serous epithelial ovarian, primary peritoneal, or fallopian tube cancer [21]. Patients were treated with either relacorilant and nab-paclitaxel or the investigator’s choice of chemotherapy (liposomal doxorubicin, paclitaxel, topotecan, or nab-paclitaxel). The study showed that cortisol modulation with relacorilant improved median OS from 12.2 to 13.9 months and median PFS from 3.8 to 5.6 months. The safety profile in the relacorilant group was generally consistent with that of the standard chemotherapy and even showed a tendency to be numerically lower for relacorilant versus the standard, including fatigue (55.0% versus 65.0%), anemia (48.3% versus 56.7%), and neutropenia (20.0% versus 36.7%). The significance of these results is defined by the fact that it was the first randomized controlled Phase 2 trial of glucocorticoid receptor modulators in patients with ovarian cancer, including patients with primary platinum-refractory disease. The trial showed a clinical benefit for the patients without additional side effects. ATHENA-MONO, a randomized, double-blind, Phase 3 trial evaluating rucaparib (a PARP inhibitor) monotherapy against placebo as maintenance treatment following response to first-line platinum-based chemotherapy in ovarian cancer, showed increased PFS from 9.2 months with placebo to 20.2 months with rucaparib [22]. The most common TEAEs grade 3 or higher were anemia (rucaparib, 28.7% versus placebo, 0%), neutropenia (14.6% versus 0.9%), and increased ALT/AST (10.6% versus 0.9%). There was no difference between arms in quality of life as measured by the Functional Assessment of Cancer Therapy – Ovarian. The authors believed that rucaparib may represent another option for first-line maintenance PARP inhibition in all molecular subgroups and that these results will lead to the U.S. FDA and European Medicines Agency (EMA) approvals.