Dr Coleman Discusses Evolving Strategies in Platinum-Resistant Ovarian Cancer

Platinum-resistant ovarian cancer remains a difficult-to-treat disease with historically limited treatment options and poor survival outcomes. Earlier this year, the FDA approved the glucocorticoid receptor antagonist relacorilant (Lifyorli) in combination with nab-paclitaxel (Abraxane) for patients with platinum-resistant ovarian cancer, adding a new treatment option to the evolving landscape.¹

The approval was based on results from the phase 3 ROSELLA trial (NCT05257408),² which evaluated relacorilant plus nab-paclitaxel vs nab-paclitaxel alone in patients who had received 1 to 3 prior lines of therapy.² The combination significantly improved both overall survival (OS) and progression-free survival (PFS), reducing the risk of death by 35% compared with nab-paclitaxel alone (HR, 0.65; P =.0004). Median OS was 16.0 months with the combination vs 11.9 months with chemotherapy alone, while median PFS was 6.5 months vs 5.5 months, respectively.^1,2

The benefit was observed across key patient subgroups, including those previously treated with PARP inhibitors, and no biomarker selection was required, supporting broader applicability in the platinum-resistant setting. The most common all-grade adverse events included neutropenia, anemia, fatigue, and nausea.^1,2

In an interview with Targeted Oncology, Robert L. Coleman, MD, Texas Oncology, discussed the evolving treatment landscape in ovarian cancer and emphasized that the relacorilant-based strategy may represent “a new regulatory bar” for future therapies in platinum-resistant ovarian cancer because of the magnitude of benefit observed over historical chemotherapy standards.

Targeted Oncology: The mechanism behind glucocorticoid receptor blockade in ovarian cancer is relatively novel. How long has the field understood cortisol signaling as a driver of platinum resistance?

Robert Coleman, MD: The biology itself is not actually new. We’ve known for many years that glucocorticoids affect tumor biology and can suppress apoptosis, which is one of the key mechanisms chemotherapy relies on to kill cancer cells. The challenge is that steroids are also extremely useful in oncology practice because they help manage infusion reactions, nausea, vomiting, and other chemotherapy-related adverse effects.

In ovarian cancer, particularly in the platinum-resistant setting, weekly taxane-based regimens have emerged as some of the most active therapies we have. But taxanes traditionally require steroid support because hypersensitivity reactions can be significant. What became important here was the opportunity to pair glucocorticoid receptor inhibition with a chemotherapy agent that does not require the same steroid support. That combination created what is essentially an ideal therapeutic partnership.

The glucocorticoid receptor is overexpressed in ovarian cancer and counteracts the apoptotic effects chemotherapy is trying to induce. Blocking that signaling pathway may allow chemotherapy to work more effectively by restoring the cell death processes we want to activate.

The ROSELLA study did not require biomarker selection, which is somewhat unusual for a targeted therapy. Does that suggest most patients with platinum-resistant disease could potentially benefit?

When we think about targeted therapy, we often think about highly specific biomarkers, but not all targeted therapies function that way. There are many therapies that target biologic processes broadly active across cancer cells rather than a mutation unique to a subgroup of patients.

Once ovarian cancer develops resistance, glucocorticoid receptor signaling becomes part of the underlying biology driving that resistance. Because of that, it was not necessary to identify a separate biomarker population. The pathway is essentially active as part of the resistant phenotype itself.

Where do you see this strategy fitting into the current treatment sequence for platinum-resistant ovarian cancer?

A large part of where this regimen fits depends on where weekly taxane strategies already fit into practice because that remains the foundation of treatment. We already have several approaches involving weekly paclitaxel, including paclitaxel alone, paclitaxel with bevacizumab [Avastin], and more recently combinations involving immunotherapy.

What is important about this regimen is that it potentially applies to a broader population. Some patients are not candidates for bevacizumab, while others may not be appropriate for immunotherapy. This combination may offer another option without some of those restrictions.

We also looked closely at prior PARP inhibitor exposure and did not see evidence that it negatively affected efficacy. By the time patients develop chemotherapy-resistant disease, many of the biologic vulnerabilities that made PARP inhibitors effective have already been overcome, so we did not necessarily expect prior PARP exposure to alter outcomes substantially.

The study reported dose interruptions and growth factor support requirements. What should community oncologists know about managing these patients in practice?

This is a heavily pretreated patient population, so supportive care requirements are very common regardless of the regimen being used. Bone marrow suppression is something we routinely manage in ovarian cancer after multiple prior lines of therapy.

The use of growth factor support and dose modifications is not unique to this regimen. We see similar considerations with many chemotherapy agents used in recurrent ovarian cancer, including taxanes, gemcitabine, and pegylated liposomal doxorubicin.

The goal is to maintain dose intensity and keep patients on schedule because repeated weekly exposure is important to how these therapies work. Fortunately, we have decades of experience managing taxane-based regimens, so these supportive strategies are very familiar to oncology practices.

Does glucocorticoid receptor blockade create concerns about adrenal insufficiency in routine practice?

That has not been a major issue with the dose and schedule used in this setting. The therapy is administered in a short pulse around chemotherapy administration, specifically the day before, the day of, and the day after treatment.

In clinical practice and throughout the trial experience, we have not seen patients developing clinically meaningful adrenal insufficiency states from this schedule. As with any chemotherapy treatment, we still evaluate patients carefully before infusion and monitor for acute illness, but this particular concern has not emerged as a major clinical problem.

How do you explain the magnitude of benefit from these newer therapies to patients?

That can actually be one of the most difficult conversations because patients experience treatment individually, while clinical trial data reflect population-level outcomes.

The easiest concept for patients to understand is lack of progression. In practice, what patients care about most is whether they are able to stay on therapy and avoid disease progression. If a patient’s disease is stable, we continue treatment because preventing progression is a meaningful outcome.

When we discuss hazard ratios, we are really talking about reductions in the probability of progression or death over time. A hazard ratio around 0.7 translates to roughly a 30% reduction in the risk of progression or death at a given point in time. That represents a meaningful improvement over historical chemotherapy standards.

Importantly, these newer strategies are beginning to outperform older benchmarks in platinum-resistant ovarian cancer, and that may ultimately change what future therapies need to compete against in clinical trials.

What message would you like community oncologists to take away as the ovarian cancer treatment landscape continues to evolve?

The landscape is changing rapidly, and for decades we had very little to offer this patient population. Now we are beginning to see therapies that produce measurable improvements not only in progression-free survival but also in overall survival.

That represents a major shift for ovarian cancer treatment. These therapies should remain top of mind for community oncologists because this area will continue evolving quickly. The more awareness there is, the more opportunities patients will have to access treatments that are making a real difference in outcomes.

REFERENCES

1. Coleman RL, Herzog TJ, Moore KN, et al. Relacorilant plus nab-paclitaxel in platinum-resistant ovarian cancer: results from the phase 3 ROSELLA trial. Presented at: 2026 Society of Gynecologic Oncology Annual Meeting; 2026.

2. ClinicalTrials.gov. Study of relacorilant plus nab-paclitaxel in patients with platinum-resistant ovarian cancer (ROSELLA) (NCT05257408). Updated April 2026. Accessed May 7, 2026. https://clinicaltrials.gov/study/NCT05257408