Novel Regimen Boosts Survival for Recurrent Platinum-Resistant Ovarian Cancer

SAN JUAN, PUERTO RICO — A novel regimen for platinum-resistant ovarian cancer solidified its role as a treatment option with a significant improvement in overall survival (OS), according to a ROSELLA trial update.

Adding the glucocorticoid receptor antagonist relacorilant (Lifyorli) to nab-paclitaxel improved median overall survival (OS) by 4 months versus nab-paclitaxel alone. The regimen received FDA approval in March on the basis of an improvement in progression-free survival (PFS).

“It is very exciting to see that the benefit was not limited to one or a few groups,” said Alexander Olawaiye, MD, of the University of Pittsburgh, at the Society of Gynecologic Oncology (SGO) meeting. “It was seen in all key subgroups, including subgroups with high-risk prognosis, those who have had PARP inhibitor therapy, and those who had short platinum intervals.” The data were simultaneously published in The Lancet.

“We are delighted to present this regimen as an option for treatment of patients with platinum-resistant ovarian cancer,” he added. “It is now listed as a preferred option in the National Comprehensive Cancer Network guidelines.”

Standard treatment for ovarian cancer, particularly platinum-resistant disease, has a “profound need” for novel therapies, such as relacorilant, said SGO invited discussant Roisin O’Cearbhaill, MD, of Memorial Sloan Kettering Cancer Center in New York City.

“The key question remains, are we meaningfully improving survival or are we just looking through a different lens — perhaps a better lens — to refine our patient selection, and are we choosing the right patient for the right treatment,” she said. “The good news is that this is a rapidly evolving space, and we do indeed have many targeted therapies on the horizon.”

The ROSELLA trial of relacorilant recruited patients who received as many as three prior lines of therapy. The addition of the glucocorticoid receptor antagonist to taxane chemotherapy showed potential for overcoming chemoresistance, O’Cearbhaill continued. Adoption of a new targeted therapy will likely involve a learning curve to optimize results. Taking into account the patient’s voice and preferences will become increasingly important as new therapeutic options arise for discussion.

Learning how to sequence new options, such as the relacorilant regimen and the recently approved KEYNOTE-B96 regimen containing pembrolizumab (Keytruda), and those yet to come will pose a challenge that requires careful consideration, including patient discussions.

“I think the take-home message here is there is no standard, dominant sequencing approach for platinum-resistant ovarian cancer,” said O’Cearbhaill. “We really have to very carefully think about the patient in front of us in our clinic, and how and which of these many options to use and in which best sequence. We have many predictive biomarkers, and they do help for a small selection of patients. However, for the vast majority of patients, our selection of chemo is still very empiric.”

“We desperately need better biomarkers to really select out those patients who are most likely to derive benefit from a given therapy,” she added. “It does appear that that glucocorticoid receptor, which is almost universally expressed across many histologies, won’t be a useful biomarker, and therefore, what we really need is novel, functional dynamic assays across multiplex panels, where transcriptional signatures will really tease out whether or not that pathway is active and whether it’s appropriate for the patient.”

As previously reported, the ROSELLA trial showed that adding relacorilant to nab-paclitaxel improved PFS by 1 month (6.54 vs 5.52 months), which proved to be statistically significant. Investigators enrolled patients with epithelial ovarian, primary peritoneal, or fallopian tube cancer that progressed less than 6 months after the last dose of platinum therapy, and a maximum of three prior lines of therapy.

The trial had dual primary endpoints of PFS and OS, and data analysis was done in 381 randomized patients. The updated results showed that median OS improved from 11.9 months with nab-paclitaxel to 16.0 months with the addition of relacorilant. The difference translated into a 35% reduction in the survival hazard (95% CI 0.51-0.83, P=0.0004). Landmark OS analyses favored relacorilant at 12 months (60% vs 50%) and 18 months (46% vs 27%). An extensive subgroup analysis showed no patient group that derived more benefit from the control regimen.

A similar proportion of patients randomized to relacorilant or nab-paclitaxel monotherapy received subsequent anticancer therapies (67.6% vs 72.0%).

Grade ≥3 adverse events (AEs) and serious AEs occurred more often in the relacorilant arm (74.5% vs 59.5%, 35.1% vs 23.7%, respectively). Deaths during treatment or within 30 days after last dose occurred in 5-6% of patients in each treatment group. No relacorilant-related fatal AEs occurred.

Anemia and neutropenia “appeared” to be worse in the relacorilant arm because patients randomized to the novel agent were exposed to treatment much longer because they were doing better, said Olawaiye. After adjustment for exposure duration, the rates were similar in the two treatment arms.