Maurie Markman, MD, leads a discussion on the design and results of the PRIMA trial, and how it has impacted practice.
Now we turn our attention to talk a little bit about some of the individual trials that are just really shaking up, is a perfectly reasonable term to use, the world of ovarian cancer management. Some of these have been published. Not all of them have published but they’ve at least been presented at major international meetings. The first study I’ll ask Dr. Naumann to speak about is the PRIMA trial.
R. Wendel Naumann, MD: So the PRIMA trial was a trial of niraparib in patients we would consider generally high risk. They had residual disease after primary surgery. They did HRD testing and these patients got up to three years of niraparib based on the study design. They were randomized at the end of chemotherapy, so they had to have had a response to chemotherapy. And this showed a benefit actually in the intent-to-treat group as well as the HRD-positive group. And, actually, when they did the subanalysis, it showed a benefit in the HRD-negative group. All of the magnitude of that benefit was relatively small. The hazard ratio is 0.68 and that translated to a median of about just under three months of benefit. But we do see a tail in that group, so I guess the question is in that subgroup, because the overall trial was positive, is that a place where PARP inhibition would be reasonable or not. And I think that’s a counseling issue based on the HRD testing.
Michael Birrer, MD, PhD: Yeah. I think one way to look at the PRIMA study is really, is an up front version of the NOVA study. This is really designed very, with NOVA being platinum-sensitive recurrence. It’s a very well conducted study. I’m not completely convinced of the HR proficient group, but my sense is they’re going to get approval for everything.
R. Wendel Naumann, MD: Yes.
Maurie Markman, MD: This is such an important question of it does appear in all of the trials that the BRCA-mutated, if you can document that, they do the best as a group. The HRD-positive, non-BRCA-mutated do second best. And whether it’s HRD-negative or proficient, whatever you want to call it, it still show a statistically significant improvement with treatment compared to the control. Whether it’s .3, to .5, to .7 hazard ratios, it’s somewhere in that range. And so then the question becomes 1) What is the FDA going to decide in the front setting. We already know what they’ve decided in the recurrent setting. But does it make a difference? I mean, should all patients get it or not get it? I’m going to just ask an opinion on that because it is such an important question. Because it seems to be almost universally that we see this change and yet it’s not a truly negative.
Michael Birrer, MD, PhD: Yeah, as usual you’ve clarified it. I mean, it’s usually in the sense of the way you rank them. If you look at the BRCA patient population, it’s just remarkable how consistent the hazard ratios are. They’re all .25 to .3. But you’re right, I don’t think it comes an issue whether someone should get a PARP or not. It relates more to sequence and timeline. I think the BRCA-mutated patients, the HRD patients are going to see these drugs earlier, and I think the wild-type patients or the HR proficient patients may see BEV instead and maybe get their PARP later on because the impact is a little bit less. That’s the way I look at it.
R. Wendel Naumann, MD: Well, I think it’s a conversation that you need to have with the patient. And it’s a conversation that probably needs to happen before they finish their chemotherapy about that preferably with the HRD testing in hand. So you can counsel them on the magnitude of the benefit and talk about the side effects of these drugs based on the benefit that we’ll get.