PARP Inhibition in Ovarian Cancer: BRCA-Mutated and Beyond - Episode 5

Antiangiogenic Therapy in Ovarian Cancer Management

November 18, 2019

Bradley J. Monk, MD, FACOG, FACS:Dr Herzog chaired a FDA consensus panel. We—he and I and others—felt that if we were going to bring drugs to you, we had to get agreement with the FDA, what are the end points? So he chaired a panel that said that progression-free survival [PFS] is an acceptable end point. It used to be it had to be survival. But we all agree that these patients are living a long time, post-progression survival is long, and that led to the FDA approval in June of 2018 of bevacizumab. It was approved in 2011 in Europe, but we had to get past this with Dr Herzog’s leadership to PFS. Tell us about that FDA approval of bevacizumab. It was a year and a half ago.

Thomas J. Herzog, MD:Yes, it was over 1800 patients, approved in frontline, as you said. We had previous approvals in platinum-resistant cancer based on the AURELIA data. And then based on OCEANS and GOG-213, we had approval in platinum-sensitive. So impressive hazard ratios, right? And in the recurrent setting, the hazard ratios are not as robust in the frontline setting. So people argue, “Well, should I use it upfront? Should I wait and use it?” And people have that argument all the time. We’ve had 2 subgroup analyses. One was from ICON7, which looked at a lower dose for a shorter period, but nonetheless showed a subgroup that truly benefited from having bevacizumab onboard.

And then we had a subgroup analysis with GOG-218. There were slightly different criteria that showed a benefit basically in the high-risk patients: stage III/IV, ascites, widespread carcinomatosis, the ones who we knew were going to recur. But what we’re learning is most of these patients are going to recur anyway. So I’m not sure there’s a low-risk advanced stage ovarian cancer population.

Bradley J. Monk, MD, FACOG, FACS:In September,Journal of Clinical Oncology, I was the last author, we showed 10 months’ improvement in overall survival for stage IV disease. Remember, I’m the expert here. I learned the technique. Exploratory end point, definitive conclusion, cross-trial comparison—I’m joking. But there is a consistency of the data between ICON7. Do you buy that, that large volume tumors do better with bevacizumab?

Thomas J. Herzog, MD:Well, I think so. And in my practice, I always use it if there’s any component of significant ascites, and certainly pleural effusions in a large volume disease. I find that it helps those patients significantly. Those who start with large volume ascites….

Bradley J. Monk, MD, FACOG, FACS:They’re in trouble and they need it.

Thomas J. Herzog, MD:They’re in trouble, and it’s amazing how fast they can dry that up.

Bradley J. Monk, MD, FACOG, FACS:Ascites, as we’ve talked about before, is angiogenesis out of control. These new blood vessels are not completely tubularized, and they extravasate fluid into the peritoneal cavity. That’s ascites. So it is a surrogate biomarker for angiogenesis out of control. And I agree with that. I probably use a little bit more bevacizumab than you. But again, we’ve been in this since of June 2018.

Thomas J. Herzog, MD:It’s been a moving target though in terms of prevalence because it was under 20% before the approval, and now it’s certainly gone up significantly.

Transcript edited for clarity.