Ursula A. Matulonis, MD, and Nicoletta Colombo, MD, on Ovarian Cancer: Overall Survival Data on Relacorilant Plus Nab-Paclitaxel
2022 ASCO Annual Meeting
Ursula A. Matulonis, MD, of Dana-Farber Cancer Institute, and Nicoletta Colombo, MD, of the University of Milan and the European Institute of Oncology, discuss phase II results on the overall survival benefit of intermittent relacorilant, a selective glucocorticoid receptor modulator, combined with nab-paclitaxel, compared with nab-paclitaxel alone in patients with recurrent platinum-resistant ovarian cancer. A phase III trial comparing intermittent relacorilant plus nab-paclitaxel with investigator’s choice of chemotherapy in primary platinum-refractory disease is ongoing (Abstract LBA5503).
Disclaimer: This video transcript has not been proofread or edited and may contain errors.
Ursula Matulonis: Nicoletta great to see you. Congratulations on this study. It's a really fascinating study with really intriguing results. Can you tell us about the mechanism of action of Relacorilant and how it inhibits ovarian cancer growth?
Nicoletta Colombo: It has been shown that cortisol main use chemotherapy resistance by interfering with some apoptotic pathways, which cytotoxic agents such as Nab-Paclitaxel utilize. So basically Relacorilant is a selective glucocorticoid receptor modulator, and binds to the GI, the glucocorticoid receptor and suppresses the activity of cortisol. So in this way, of course, cytotoxic agents, such as Nab-Paclitaxel may use their apoptotic pathways and induce apoptosis and cells deaths. So that's the rational for using this drug in ovarian cancer patients.
Ursula Matulonis: Yeah. It's a really unique, unique mechanism of action that I don't think's really been tested before.
Nicoletta Colombo: No, it's really unique. It's very interesting because even very low level of cortisol may really induce chemotherapy resistance. So by suppressing this activity of cortisol, we may enhance the efficacy of cytotoxic agents.
Ursula Matulonis: And in this trial, so there were three arms. There was control Nab-Paclitaxel and then two different schedules of Relacorilant added to Nab-Paclitaxel. Can you just, did you talk about those two different schedules and why they were tested?
Nicoletta Colombo: Yeah. One schedule was just very, I mean, low level of continuous Relacorilant and the other one was Relacorilant given the day before, the day off, and the day after chemotherapy. Why that? Because on one end, continuous administration may provide a continuous antagonist of cortisol, but on the other hand, by giving higher dose of Relacorilant around times of maximum chemotherapy exposures may provide a better antagonist. So that's why we decided to use or to test these two different schedules.
Ursula Matulonis: Yeah. Gotcha. And tell us about the results which are intriguing and I think really promising.
Nicoletta Colombo: Yeah, this is a randomized phase two, and we enroll 178 patients in these three arms. So the comparator arm, which was Nab-Paclitaxel alone given the day 1, 8, 15 of a 28 day cycle. And then we have the two Relacorilant arm, the intermittent and continuous. These patients were really very heavily retreated patients up to five prior lines of chemotherapy. All but one had received prior taxane. More than 50% had received bevacizumab. And about one third had received even PARP inhibitors, so really a very, very heavily pretreated population. Moreover, 36% had a platinum refractory disease, and some of them even primary platinum refractory disease. And actually there was an unbalance on the percentage of patients with primary platinum refractory disease, which was higher in the intermittent scheduling arm. So, so patients were randomized in these three arms, and then the primary endpoint was progression free survival. And we presented already the data at ESMO last year, and we demonstrated a significant improvement in progression free survival for patients receiving the intermittent schedule of Relacorilant. And so this was the primary endpoint, but today, I mean at this conference, I will present the overall survival data. And it's very interesting because already at that time, we saw a trend for an improvement in overall survival. And this trend has been now confirmed. Actually, we see that for the intermittent schedule compared to the standard arm, we have a hazard ratio 0.67, which does not reach really statistically significant, but is very close. But what we did the scenes, as I said, there was an imbalance in the primary platinum refractory patients population, we perform subgroup analysis taking away the primary platinum refractory. And in this situation, the hazard ratio is 0.63 and becomes statistically significant. So I think this is a great news because we know that patients with platinum resistant ovarian cancer represent a very high unmet need. And we now have a completely different drug with a very unique mechanism of action, which can potentiate the efficacy of chemotherapy.
Ursula Matulonis: Incredibly exciting. What's the future for the drug? What are your next plans?
Nicoletta Colombo: Yeah, of course. One thing I didn't say is that also the toxicity profile was quite good. And, we did not observe any increase in toxicity, even though I must say all patients receive prophylactic GCSF, but also in the comparator arm, 46% receive GCSF. So drug, well tolerated. Quality of life data very good, no, no detrimental effect. And that's why we want to do a prospective randomized phase three study. And this is planned, and we'll start at the end of the year. It's called ROSELLA. And so more than 300 patients, 360 patients will be randomized to receive Relacorilant plus Nab-Paclitaxel. Theirs is a physician choice chemo could be taxane, Nab-Paclitaxel, or liposomal doxorubicin. And the primary point will be investigator assessed progression free survival. And of course also a key secondary endpoint will be overall survival.
Ursula Matulonis: Yeah. Awesome. Congratulations again. Really wonderfully conducted trial and really promising results. So thank you so much.
Nicoletta Colombo: Thank you. Thank you. Thank you very much.
The ASCO Post Staff
Benoit You, MD, PhD, of Lyon University hospital (HCL, France) and GINECO group (France), discusses findings from the GOG-0218 trial of patients with ovarian cancer, which appears to confirm earlier data on the link between poor tumor chemosensitivity and benefit from concurrent plus maintenance bevacizumab. In Dr. You’s validation study, patients who derived the most progression-free and overall survival benefit from bevacizumab were those with high-risk disease (stage IV or incompletely resected stage III) associated with an unfavorable KELIM score (CA-125 kinetic elimination rate constant, calculable online) (Abstract 5553).
The ASCO Post Staff
Stephen M. Ansell, PhD, MD, of Mayo Clinic, discusses updated data from the ECHELON-1 trial, which showed that, when administered to patients with stage III or IV classical Hodgkin lymphoma, the combination of brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine (A+AVD) vs doxorubicin, bleomycin, vinblastine, and dacarbazine resulted in a 41% reduction in the risk of death. These outcomes, says Dr. Ansell, confirm A+AVD as a preferred option for previously untreated disease (Abstract 7503).
The ASCO Post Staff
Lisa A. Carey, MD, of the University of North Carolina Lineberger Comprehensive Cancer Center, and Shanu Modi, MD, of Memorial Sloan Kettering Cancer Center, discuss the phase III findings from the DESTINY-Breast04 trial, which compared fam-trastuzumab deruxtecan-nxki (T-DXd) vs treatment of physician’s choice (TPC) in patients with HER2-low unresectable and/or metastatic breast cancer. T-DXd is the first HER2-targeted therapy to demonstrate clinically meaningful improvement in progression-free and overall survival compared with TPC in this patient population, regardless of hormone receptor or immunohistochemistry status or prior use of CDK4/6 inhibitors (Abstract LBA3).
The ASCO Post Staff
Georgina V. Long, MD, PhD, of the Melanoma Institute Australia, The University of Sydney, discusses phase III findings from the KEYNOTE-716 study. The trial showed that compared with placebo, adjuvant pembrolizumab significantly improved distant metastasis–free survival in patients with resected stage IIB and IIC melanoma. The findings also suggest a continued reduction in the risk of recurrence and a favorable benefit-risk profile (Abstract LBA9500).
The ASCO Post Staff
Shilpa Gupta, MD, of the Cleveland Clinic Foundation, discusses an updated consensus definition for standard therapy and clinical trial eligibility for patients with metastatic urothelial cancer who are platinum-ineligible, criteria that are proposed to guide treatment recommendations for this population. This may be especially important now that the U.S. Food and Drug Administration has restricted the use of first-line pembrolizumab to those who are considered platinum-ineligible (Abstract 4577).