Glucocorticoid Receptor Expression and Activity in Ovarian Cancer

Platinum based chemotherapies are main stream treatment options in initial lines of therapy. Resistance towards chemotherapy in ovarian cancer is been quite frequent leading to higher recurrence rate in OC. The higher expression of glucocorticoids and subsequently, glucocorticoids (Cortisol) play a huge role in developing resistance against SOC chemotherapy. Orally available Relacorilant, a glucocorticoid receptor antagonist, upon administration, competitively binds to and blocks GRs. This inhibits the activity of GRs, and prevents both the translocation of the ligand-GR complexes to the nucleus and gene expression of GR-associated genes. This decreases the negative effects that result from excess levels of endogenous glucocorticoids and helps in reversing chemo resistance for cytotoxic agents. In addition, by binding to GRs and preventing their activity, inhibition with relacorilant also inhibits the proliferation of GR-overexpressing cancer cells.

Interim Phase II clinical study results for intermittent relacorilant + nab-paclitaxel arm showed improved efficacy (PFS and OS) compared to the continuous relacorilant + nab-paclitaxel arm and comparator arm without the additional burden of side effects in patients with recurrent platinum-resistant ovarian, fallopian Tube, or primary peritoneal cancer. Encouraged by Phase II results, Corcept Therapeutics plans for pivotal Phase III trial in the second half of 2022.

As of now, mainstream treatment modalities have shown weaker efficacy, and caregivers feel a huge unmet need in platinum-refractory or resistant OC patients. The efficacy outlook of novel GR modulators so far has proved that it could be a breakthrough treatment option and will address a huge unmet need with a noticeably more acceptable pharmacodynamics and pharmacokinetic profile in the second or later line of therapy. Corcept Therapeutics is all set for a revelation during the conference. It will be interesting to watch the progressive outcomes of relacorilant in combination with Nab-Paclitaxel at ESMO 2022.