ROSELLA Trial Extends Survival in Platinum-Resistant Ovarian Cancer

The ROSELLA trial found that adding relacorilant to Abraxane (nab-paclitaxel) improved overall survival for patients with platinum-resistant ovarian cancer, introducing a new way to target the glucocorticoid receptor pathway, according to Dr. Alexander B. Olawaiye, director of Gynecologic Cancer Research at Magee-Womens Hospital of UPMC.

He explained that relacorilant is taken as a pill for just three days around each weekly infusion, allowing patients to take part of treatment at home. The combination showed no new side effects beyond those already known with chemotherapy. Median overall survival improved by 4.1 months, one of only two trials in this setting to show that benefit. Because the treatment does not require biomarker testing and the target pathway is present in most ovarian cancers, Olawaiye said it could expand access and offer a well-tolerated option for many patients.

CURE: For patients with platinum-resistant ovarian cancer, what does the ROSELLA trial show that is new or different from existing treatment options?

Olawaiye: Well, many things. First, the ROSELLA trial showed that we can modulate the steroid receptor pathway, specifically the glucocorticoid receptor, and gain benefit in the treatment of platinum-resistant ovarian cancer. This is the first time this has ever been shown in cancer, and particularly in ovarian cancer, because of the uniqueness of the pathway. This is very new in every way you can imagine. That’s number one.

Number two is that the relacorilant medication we studied in the trial is a pill. It’s not taken every day of the cycle. It’s taken only for three days around the infusion. So there are two medications in the regimen. There’s a medication called Abraxane, which is an infusion patients receive once a week. Then, the day before the infusion, they take a relacorilant pill, another pill on the day of the infusion and a pill the day after. That’s it, just those three days. That convenience is unique because patients can take it at home.

The third thing that was unique is that we were really surprised that the only toxicities we saw on the trial were toxicities we already know are associated with Abraxane. There was no unique toxicity we could attribute to relacorilant itself, so it’s uniquely nontoxic.

The study showed a 4.1-month improvement in median overall survival. How do you help patients understand what that could mean for them personally?

Yes, so when we do trials, there are two very important outcome measures. One is progression-free survival, which is how long from the time a patient starts treatment before the cancer begins to grow again. That’s important.

But even more important is overall survival, meaning whether the total length of time a patient lives is extended by the treatment.

Progression-free survival is commonly achieved in many clinical trials. Only a very few trials actually achieve an extension of overall survival. In platinum-resistant ovarian cancer, this is only the second published trial to show that. The first one is MIRASOL. ROSELLA is the second that achieved this outcome. There is one other trial that has claimed it, but it hasn’t been published. So if you think about how many studies there are in platinum-resistant ovarian cancer — maybe more than 100 — and only two have shown an overall survival benefit, that’s very significant.

The trial did not require biomarker testing. How does that potentially affect access and decision-making for patients?

It’s positive on both fronts because we have some great medications that are newly approved for platinum-resistant ovarian cancer. One is Elahere (mirvetuximab soravtansine) from the MIRASOL study and the other is trastuzumab deruxtecan from the DESTINY-PanTumor02 trial.

Both are great drugs, but patients must have specific biomarkers. For Elahere the cancer must express high levels of folate receptor alpha. If the tumor doesn’t have that expression, the patient can’t receive the drug. Trastuzumab deruxtecan is also biomarker-based. The tumor must express HER2 at a certain level. So although these are excellent treatments, they don’t apply to the majority of patients.

Those restrictions are not associated with relacorilant. It modulates the glucocorticoid receptor pathway, and that receptor is expressed in over 95% of ovarian cancers. We also looked at whether the level of expression mattered, and it didn’t. Regardless of expression level, patients were able to benefit.

From what you observed personally in the trial, what was the treatment experience like for patients receiving the combination?

Very well tolerated. It’s one of those what I call magical combinations that we look for in oncology. The drug is working and the patient isn’t suffering from excessive toxicities. You couldn’t ask for anything better.

When we closed the phase 2 trial before phase 3, some of my colleagues were actually asking me to expand enrollment because they had patients lined up. That was because they could see the drug was working and patients weren’t struggling with side effects.

There were toxicities from Abraxane, of course. It’s still chemotherapy. But those were the only ones we saw. There was nothing we could uniquely blame on relacorilant.

As this therapy is under FDA review, what should patients be discussing now with their care teams while waiting for a decision?

Most patients with platinum-resistant ovarian cancer would likely be eligible if it’s approved. In ROSELLA, we allowed up to three previous lines of therapy, and many patients received it as a fourth line and still benefited.

We also saw benefit in groups that are usually harder to treat, like patients who had prior PARP inhibitors. Often those patients don’t respond as well to the next therapy, but we didn’t see that problem here.

Another thing we noticed was ascites. Many patients with recurrent disease struggle with fluid buildup in the abdomen. On the relacorilant arm, ascites issues were less frequent, which was nice to see.

Transcript has been edited for clarity and conciseness.

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