Dr Lorusso on the Use of Selective Glucocorticoid Receptor Modulators in Recurrent Ovarian Cancer

Domenica Lorusso, MD, PhD, director, Gynaecological Oncology Unit, Humanitas Hospital San Pio X, Milan; full professor, Obstetrics and Gynaecology, Humanitas University, discusses the rationale for investigating the selective glucocorticoid receptor modulator relacorilant (CORT125134) alongside nab-paclitaxel (Abraxane) in recurrent, platinum-resistant ovarian cancer.

Emerging preclinical and early clinical evidence has revealed that the overexpression of the glucocorticoid receptor in solid tumors correlates with poor prognosis, Lorusso begins. This overexpression is believed to contribute to chemoresistance and the promotion of epithelial-mesenchymal transition, a process that accelerates tumor progression and resistance to chemotherapy, she explains. Notably, this phenomenon has been observed in various solid tumors, including ovarian cancer, Lorusso adds.

Selective glucocorticoid receptor modulation with relacorilant has shown potential for reversing chemoresistance and improving the efficacy of chemotherapy, Lorusso continues. A phase 1/2 trial (NCT02762981) evaluated the safety and efficacy of relacorilant in combination with nab-paclitaxel in patients with solid tumors as did a phase 2 trial (NCT03776812) in patients with recurrent, platinum-resistant ovarian cancer. Nab-paclitaxel was chosen because it does not require prior treatment with a glucocorticoid, which could undermine the therapeutic effectiveness of relacorilant, Lorusso notes. The latter trial demonstrated that the use of relacorilant plus nab-paclitaxel had an additive effect on treatment efficacy, suggesting that this combination may improve patient outcomes, she reports.

These early results suggest that this combination could help restore chemosensitivity and enhance the overall response to chemotherapy in patients with glucocorticoid receptor–overexpressing tumors, Lorusso concludes. The phase 3 ROSELLA trial (NCT05257408) is underway to further assess the efficacy of this combination therapy in a larger population of patients with platinum-resistant ovarian cancer. If successful, this strategy could offer a novel approach to overcoming chemoresistance in ovarian cancer.