Bradley J. Monk, MD, FACS, FACOG: Let’s transition to chemotherapy. For our audience, our specialty brought paclitaxel to the oncology world. We also have now brought you PARP inhibitors, which we will discuss soon. But chemotherapy has changed. Paclitaxel has probably been here since 1996, since the GOG 111 study. I’m struck by the recent NCCN guidelines. The NCCN guidelines were updated in March of 2018. There were a number of frontline chemotherapy changes. And what the NCCN guidelines said, at least based on my interpretation, is, how can we have a level 1 recommendation when it’s not clear through survival that it’s the best approach? Generally, level 1 is 100% no controversy.

So, they downgraded what previously had been level 1’s. Even intraperitoneal chemotherapy was downgraded from a level 1 to a level 2a. Dose-dense weekly was downgraded from a level 1 to a level 2a. But also, bevacizumab was upgraded from a level 2b to a level 2a. So, there was harmonization because it’s just not that clear. They were all basically acceptable. I think we can agree on that—with the options that I just described.

I think that the evolution has been seen with the filing to the FDA. They filed in August, and there’s a PDUFA date set up for frontline bevacizumab, for June of 2018. Frontline bevacizumab has been approved around the world, basically, but not here, really from a historical trial that published in the New England Journal of Medicine in 2011. Can you tell us about this trial (GOG-0218), which has been around for a long time but was just filed with the FDA and now is even upgraded by the NCCN from a level 2b to a level 2a?

Matthew Powell, MD: Well, I want to respond to the NCCN difference. One of the issues had to do with now adding evidence blocks into the NCCN. I think it’s value-added. That changed some of the way we present, on your sheet, looking back at cost, toxicity, and all of these other considerations. Hopefully, this provides NCCN guidelines readers with a little more information, when we use the evidence blocks. I think that may have been part of the change in strategy, in how things move from a category 1 to a category 2.

That being said, we’re talking about GOG-0218. And, as you mentioned, ICON7 and GOG-0218 were published back-to-back in the New England Journal of Medicine, back in 2011. We know that bevacizumab is an active drug in ovarian cancer. I think that several of us were quite surprised when the initial experience with GOG-0218 didn’t show as much benefit as we all would have predicted. ICON7 certainly showed that trend towards overall survival benefit in the high-risk population—the suboptimally debulked stage 3 and stage 4 patients. So, we kind of know that this is a little bit of a biomarker on who may benefit.

And now, with the upcoming data to be presented at the ASCO Annual Meeting, we think there’s going to be data on overall survival, mature for GOG-0218. You know that the progression-free survival matured back in 2011. Finally, matured overall survival data will be presented. I don’t know those data, but I think we’ll find out about them in June. I understand that the FDA has set up a PDUFA date, at the end of June, for looking at this question.

When we look at back, originally in GOG-0218, we saw that 5-month or 4-month difference in progression-free survival in the population that got bevacizumab with their chemotherapy, followed by a maintenance strategy afterwards. That was the group that seemed to have the most benefit.

Transcript Edited for Clarity