The efficacy of relacorilant, a glucocorticoid antagonist, has raised concerns that routine steroid use with chemotherapy may induce resistance. This has led clinicians to reduce steroid doses, questioning a long-standing practice and its potential to blunt the therapeutic effects of chemotherapy.

The persistent separation of survival curves in the ROSELLA trial suggests relacorilant's benefit extends beyond sensitizing tumors to chemotherapy. By acting as a glucocorticoid receptor antagonist and blocking immunosuppressive cortisol, it may also have a favorable immune-modulatory effect.

The ROSELLA trial's success in boosting chemotherapy with a glucocorticoid receptor antagonist is thought-provoking. It suggests that routinely used steroids for managing side effects like nausea might inadvertently be diminishing chemotherapy's effectiveness across various cancers.

The novel drug relacorilant overcomes taxane resistance in ovarian cancer by targeting glucocorticoid receptors. It blocks stress-induced steroid signaling that promotes anti-apoptotic proteins, effectively re-sensitizing tumors to chemotherapy. This represents a completely new mechanism of action for this patient population.

While PARP inhibitors show some effect in all patients, clinical data revealed a significant survival advantage only in the HRD-positive subgroup. This has led to an FDA restriction, making biomarker testing a prerequisite for this class of drugs.

While RAS/MAP kinase alterations typically signify a more aggressive cancer with lower chemotherapy response, there's a notable exception. In low-grade serous ovarian cancers, patients with KRAS alterations may actually have a slightly better prognosis. This nuanced finding challenges the broad assumption that all RAS pathway mutations are purely negative prognostic markers.

The glucocorticoid receptor antagonist relacorilant does not require biomarker testing for patient selection. Its target is ubiquitously expressed in over 95% of ovarian cancer tissues, making it a broadly applicable therapy without the need for additional screening.

Despite stratifying patients by PD-L1 status, the AGO-OV-229 trial found it was not a predictive marker. Hazard ratios for survival were similar for both PD-L1 positive and negative tumors, challenging its utility for patient selection.

High cortisol, a stress hormone, is linked to worse outcomes in ovarian cancer. Relacorilant, by blocking its receptor, appears to overcome chemo resistance by allowing the body's own immune system to help fight the cancer.