SAN JUAN, Puerto Rico – A novel regimen for platinum-resistant ovarian cancer has solidified its role as a treatment option with significant improvements in overall survival (OS), according to a ROSELLA trial update.
Adding the glucocorticoid receptor antagonist Relaxorilent (Lifiorli) to nab-paclitaxel improved median overall survival (OS) by 4 months compared to nab-paclitaxel alone. The regimen received FDA approval in March based on improvements in progression-free survival (PFS).
“It’s very exciting to see that the benefit was not limited to one or a few groups,” Alexander Olawiye, MD, of the University of Pittsburgh, said at the Society of Gynecologic Oncology (SGO) meeting. “This was seen in all major subgroups, including those with a higher risk prognosis, those who had PARP inhibitor therapy, and those who had a shorter platinum interval.” The data was published together The Lancet.
“We are pleased to offer this regimen as an option for the treatment of patients with platinum-resistant ovarian cancer,” he said. “It is now listed as a preferred option in the National Comprehensive Cancer Network guidelines.”
There is a “deep need” for innovative treatments such as relacoreliant, especially for platinum-resistant disease that is standard treatment for ovarian cancer, said SGO invited discussant Roisin O’Seirebhail, MD, of Memorial Sloan Kettering Cancer Center in New York City.
“The key question is whether we are meaningfully improving survival or we are just looking through a different lens – perhaps a better lens – and whether we are selecting the right patient for the right treatment,” he said. “The good news is that this is a rapidly developing field, and we actually have several targeted therapies on the horizon.”
The Rosella trial of Relaxorilent enrolled patients who had received at least three prior lines of therapy. O’Cearbhaill continued, adding glucocorticoid receptor antagonists to taxane chemotherapy showed potential to overcome chemoresistance. Adoption of a new targeted therapy is likely to involve a learning curve to optimize outcomes. As new therapeutic options come up for discussion, it will become more important to take into account the patient’s voice and preferences.
Learning to sequence new options, such as the relaxer regimen and the recently approved KEYNOTE-B96 regimen that includes pembrolizumab (Keytruda), and those yet to come, will pose a challenge that requires careful consideration, including patient discussion.
“I think the message here is that there is no standard, effective sequencing approach for platinum-resistant ovarian cancer,” O’Seirebhail said. “We really have to think very carefully about the patient in front of us in our clinic, and how and which of these many options to use and in what best order. We have many predictive biomarkers, and they help for a small selection of patients. However, for most patients, our selection of chemo is still very empirical.”
“We really desperately need better biomarkers to select the patients who are most likely to benefit from a given therapy,” he said. “It appears that the glucocorticoid receptor, which is almost universally expressed in many histologies, will not be a useful biomarker, and so, we really need novel, functional dynamic assays in multiplex panels, where the transcriptional signature will actually detect whether that pathway is active and whether it is appropriate for the patient.”
As previously reported, the ROSELLA trial showed that adding relaxorient to nab-paclitaxel improved PFS by 1 month (6.54 vs. 5.52 months), which proved to be statistically significant. The investigators enrolled patients with epithelial ovarian, primary peritoneal, or fallopian tube cancer who had progressed less than 6 months after the last dose of platinum therapy, and had a maximum of three prior lines of therapy.
The trial had dual primary endpoints of PFS and OS, and data analysis was conducted in 381 randomized patients. Updated results showed that median OS improved from 11.9 months with nab-paclitaxel to 16.0 months with relacoreliant. This difference translated into a 35% reduction in survival hazard (95% CI 0.51–0.83, P=0.0004). Landmark OS analyzes preferred relocalizer at 12 months (60% vs 50%) and 18 months (46% vs 27%). A comprehensive subgroup analysis showed that there was no patient group that derived greater benefit from the control diet.
A similar proportion of patients randomized to relicorilent or nab-paclitaxel monotherapy subsequently received anticancer therapy (67.6% vs. 72.0%).
Grade ≥3 adverse events (AEs) and serious AEs occurred more frequently in the recovalent arm (74.5% vs 59.5%, 35.1% vs 23.7%, respectively). Deaths occurred in 5-6% of patients in each treatment group during treatment or within 30 days after the last dose. No relicolant-related fatal AEs occurred.
Anemia and neutropenia appear to be worse in the relapsed arm because patients randomized to the novel agent were kept on treatment longer because they were doing better, Olawaye said. After adjustment for exposure duration, rates were similar in the two treatment arms.
