Bradley J. Monk, MD: The next study that we’re going to hear about is the second strategy, adding an anti-VEGF to a checkpoint inhibitor. Tell us about your study, Katie Moore: IMagyn050.
Kathleen N. Moore, MD: IMagyn050 is a randomized phase 3 study, 2 arms. It enrolled all histologies except for mucinous, so very different from what we’ve just discussed. All of those studies—PRIMA, PAOLA-1, VELIA—are limited to high-grade serous and some high-grade endometrioid. But this allowed clear cells as well. Biomarker stratification was PD-L1, and that was an important difference between our study and JAVELIN OVARIAN 100. We are stratifying there. Then we randomized to paclitaxel, carboplatin, placebo, and placebo maintenance with bevacizumab. So everyone gets bevacizumab throughout, and then placebo, placebo maintenance, or paclitaxel, carboplatin, bevacizumab, atezolizumab; and then atezolizumab-bevacizumab maintenance. It’s a dual primary end point of progression-free and overall survival. It finished accrual in April 2019, and we are in final stages of data cleaning.
Bradley J. Monk, MD: We’re excited that it should be the next large study. Hopefully it’ll be a breakthrough.
Kathleen N. Moore, MD: I hope so too.
Bradley J. Monk, MD: Sharyn Lewin, you’re an advocate of this trial, and you enrolled in your practice called FIRST. Tell us what FIRST is.
Sharyn N. Lewin, MD: FIRST is presently open and enrolling patients. It’s a very interesting study for women with stage III and IV epithelial ovarian cancer. It’s looking at standard of care, which is paclitaxel and carboplatin IV [intravenous], interestingly with or without the bevacizumab and looking at the role of VEGF. Patients are randomized to either the dostarlimab or placebo in cycles 2 through 6 and with or without Avastin, based on your prior decision. Then there is a maintenance phase looking at either niraparib, dostarlimab, or placebo. It’s a complicated schema looking at the different formations of that. It’s just looking at the combination of dostarlimab, bevacizumab, and niraparib versus placebo.
Bradley J. Monk, MD: We’re excited, I enrolled in that too, and we’ll have to see what happens. Then I have a study called ATHENA. ATHENA is a pure maintenance trial that distinguishes itself from these other trials in the PRIMA theme where we focused on the maintenance opportunity. It is just a simple question: Should we add a checkpoint inhibitor to a PARP inhibitor? 400 patients get maintenance PARP, à la PRIMA, and that PARP inhibitor is rucaparib. Then 400 patients get nivolumab plus rucaparib, and integrated into that is a placebo. The first end point to report will be the PRIMA opportunity, just PARP versus placebo. Over time we’ll do the primary end point, which is rucaparib versus rucaparib-NIVO [nivolumab]. There is a small nivolumab arm of 100 patients. It’s 400 rucaparib, 400 rucaparib-nivolumab, 10% or 100 nivolumab, 10% placebo. This trial has finished enrollment within the United States; it’s winding down. This will probably be, at least in the rucaparib-versus-placebo arm, the next study to report after IMagyn050 in the frontline setting.
Let’s go ahead and end there. That was a comprehensive conversation about frontline treatment, really leveraging the opportunity of GOG-0218 and bevacizumab approved in June 2018, and then ultimately the opportunity for SOLO-1, PARP inhibitor and maintenance therapy, PRIMA, PARP inhibitor beyond BRCA, and then ultimately the combination PAOLA-1.
I want to quote my good friend Tom Krivak, who says, “It’s a maintenance world”—the most important thing is that maintenance is used. I’m going to quote my good friend Katie Moore, who says, “I just don’t understand why people would think that these patients with advanced ovarian cancer are cured.” There’s a synergy there that if they’re not cured, you have the opportunity to keep them in response. All these studies did not show a decrement in quality of life.
Transcript edited for clarity.