Platinum-resistant ovarian cancer gets survival boost with add-on relacorilant

Adding the first-in-class selective glucocorticoid receptor antagonist relacorilant to nab-paclitaxel results in improved survival outcomes for patients with platinum-resistant ovarian cancer, as shown in the topline results of the phase III ROSELLA study.

Over a median follow-up of 9.0 months, the median progression-free survival (PFS) assessed by blinded independent central review (BICR) increased from 5.52 months with nab-paclitaxel alone to 6.54 months with add-on relacorilant, translating to a 30-percent risk reduction (hazard ratio [HR], 0.70, 95 percent confidence interval [CI], 0.54–0.91; p=0.0076). This was consistent with investigator-assessed PFS (HR, 0.71; p=0.0030), reported first author Dr Alexander Olawaiye from the University of Pittsburgh School of Medicine in Pittsburgh, Philadelphia, US. [ASCO 2025, abstract LBA5507]

For overall survival (OS), while the data had not fully matured at the data cutoff, the combination arm had a clinically meaningful OS extension compared with the nab-paclitaxel arm (median, 15.97 vs 11.50 months), with a 31-percent reduction in the hazard of progression or death (HR, 0.69, 95 percent CI, 0.52–0.92; p=0.0121), Olawaiye continued.

At 12 months, the PFS rates were 25 percent in the combination arm and 13 percent in the nab-paclitaxel arm. The corresponding 12-month OS rates were 60 percent and 49 percent.

Olawaiye stated that the point estimates for PFS and OS were in favour of the combination in virtually all the subgroups that were analysed. “This was particularly notable in high-risk–prognosis groups, including those who had had three lines of therapy, those with prior PARP inhibitor exposure, those with short primary platinum-free interval, and those with heavy disease burden.”

Moreover, treatment with relacorilant plus nab-paclitaxel was associated with a 6.8-improvement in objective response rate (36.9 percent vs 30.1 percent; p=0.17) and 12.2-percent improvement in clinical benefit (response or stable disease maintained for 24 weeks) rate (51.1 percent vs 38.9 percent; p=0.016), he added. “This was a surprising finding, which we did not anticipate.”

As for safety, relacorilant combined with nab-paclitaxel was well-tolerated, with a favourable safety profile. Grade ≥3 adverse events (AEs) occurred in 74.5 percent of patients in the combination arm and in 59.5 percent in the nab-paclitaxel arm, while serious AEs were documented in 35.1 percent and 23.7 percent, respectively. Discontinuations of nab-paclitaxel due to treatment-emergent AEs were infrequent and similar between the two treatment arms (9.0 percent and 7.9 percent, respectively).

The most common AEs were neutropenia, anaemia, fatigue, nausea, diarrhoea, and alopecia. In particular, grade ≥3 neutropenia and anaemia occurred in 44 percent and 18 percent of patients in the combination arm, and in 25 percent and 8 percent in the nab-paclitaxel arm, respectively.

“Apparently, [the frequency of haematologic AEs] looked worse in the relacorilant arm, but remember that these patients were exposed to nab-paclitaxel therapy longer because they were doing better” compared with those in the nab-paclitaxel only arm (mean duration, 23.2 vs 18.6 weeks), Olawaiye said. “When we adjusted for the nab-paclitaxel exposure, the rate of neutropenia and anaemia in both arms of the trial were comparable.”

Finally, there were no relacorilant-related fatal AEs.

Taken together, these findings demonstrate that “intermittently dosed relacorilant plus nab-paclitaxel is an efficacious treatment regimen for patients with platinum-resistant ovarian cancer, without the need for a biomarker,” according to Olawaiye.

Ovarian cancers frequently express the glucocorticoid receptor (GR), a marker linked to a poor prognosis. This is because GR signalling can reduce cancer cells’ sensitivity to chemotherapy, the author explained. Relacorilant addresses this by restoring the tumours’ sensitivity to cytotoxic chemotherapy.

“We believe relacorilant plus nab-paclitaxel should be the new standard for platinum-resistant ovarian cancer therapy,” he concluded.

Emerging treatment options

Meanwhile, study discussant Dr Debra Richardson from the Stephenson Cancer Center at the University of Oklahoma in Oklahoma City, Oklahoma, US, pointed to the relacorilant plus nab-paclitaxel as a “new treatment option” for platinum-resistant ovarian cancer, while noting another efficacious treatment regimen.

Specifically, in the phase III KEYNOTE-B96, pembrolizumab in combination with paclitaxel with or without bevacizumab prolonged the primary endpoint of PFS in patients with platinum-resistant recurrent ovarian cancer whose tumours expressed PD-L1 and in all-comers, as well as the secondary endpoint of OS in patients with tumours expressing PD-L1, Richardson said.

Given these developments, she raised several questions about treatment choices and sequencing: “If a patient has had prior bevacizumab, would you choose weekly paclitaxel and bevacizumab or weekly nab-paclitaxel with relacorilant after the data presented? Now that there may be two regimens with OS benefit, how will you sequence if the patient is eligible for both therapies? And if there are multiple options for antibody-drug conjugates, which there will be, what is the best way to sequence them?”

ROSELLA study

Conducted at 117 sites across several countries, ROSELLA included 381 patients with platinum-resistant, epithelial ovarian, primary peritoneal, or fallopian tube cancer; up to three previous lines of anticancer therapy and previous bevacizumab exposure; and disease progression or intolerance to the most recent therapy.

The patients were randomly assigned to receive relacorilant (150 mg orally the day before, of, and after nab-paclitaxel infusion) plus nab-paclitaxel (80 mg/m² intravenously on days 1, 8, and 15 of each 28-day cycle) (n=188) or nab-paclitaxel alone (100 mg/m² intravenously on the same schedule) (n=193).

The median age of patients was 61 years in the combination arm and 62 years in the nab-paclitaxel arm, with most patients being White (72.3 percent and 69.9 percent, respectively). A total of 35.6 percent and 42.5 percent of patients in the respective arms had received at least one line of therapy in the platinum-resistant setting.

The dual primary endpoints were PFS and OS, and the study was considered positive if either of these endpoints was met.