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Maintenance Therapy: PARP Inhibitor or Bevacizumab

Panelists: Bradley Monk, MD, FACOG, FACS, St. Joseph's Hospital and Medical Center; Michael J. Birrer, MD, PhD, O'Neal Comprehensive Cancer Center; Jubilee Brown, MD, Levine Cancer Institute; Thomas Herzog, MD, UC College of Medicine; Krishnansu S. Tewari, MD, University of California, Irvine
Published: Saturday, Aug 17, 2019



Transcript:

Bradley Monk, MD, FACOG, FACS: So, Tom, there was a meta-analysis here addressing this concept of bevacizumab or PARP. I kind of like that. I know you read that and tell me what that showed.

Thomas Herzog, MD: Yeah, Brad, it was one of the papers that really caught my eye. It’s a little clever and I don’t know enough about the statistical means that were used. They used a SUCRA tool, which is to rank effect size with the surface under the cumulative ranking value that was applied. And I don’t know what that means exactly, so don’t pin me down on that. But the numbers look great. The bottom line is how do we interpret these 5 trials, right? How do we put those into practice and when do we use a PARP [poly ADP ribose polymerase] inhibitor, and when do we use bev [bevacizumab]? I think everyone on the panel, if you don’t agree, please speak up. But I think we all say that patients that are candidates for maintenance should be offered maintenance.

Bradley Monk, MD, FACOG, FACS: Yeah.

Thomas Herzog, MD: I think everyone agrees on that but what maintenance and how do we look at that. And what they tried to do is model from the 8 major trials that are out there and calculate a hazard ratio. And what they did is they looked at patients that were all-comers. And you might imagine you’re going to have a mix then of wild-type and mutations that are probably 20% or so mutations and 70%  not. But what’s more informative to me was the breakdown of the wild-type versus the BRCA-mutant. And what they did is they compared PARP versus bev, they compared PARP versus just chemo [chemotherapy] alone, or bev versus chemo alone. And for the BRCA-mutated patients, imagine of course who was going to win, it was obviously the PARP. So the PARP had 0.46 versus chemo hazard ratio is 0.25 which we already know. And bev?  also did well, hazard ratio of 0.55. Those are in the patients but not as well as the PARP in the BRCA-mutated patients.

And the wild-type saw a little bit of a diminution favoring the PARP, but it crossed 1 and it was 0.87. That’s the area that we don’t know, and that’s the biggest patient population that we have. And it still doesn’t completely decide that. But I was surprised to see it perform as well as it did. The PARP did quite well there. PARP did much better as did bev versus traditional chemo.

Bradley Monk, MD, FACOG, FACS: But this all fits now.

Thomas Herzog, MD: Yes.

Bradley Monk, MD, FACOG, FACS: So we said that probably most patients should get bev in frontline therapy, and if you got bev in the frontline, when you have a platinum-sensitive relapse, which almost all patients do, because you got bev and it extends the platinum-free interval, then you should get PARP inhibitor in the second line.

Thomas Herzog, MD: Yeah.

Bradley Monk, MD, FACOG, FACS: So that meta-analysis supports I think what we’re doing—bev for frontline therapy, PARP inhibitor second-line maintenance unless you’re BRCA-mutated, then you get olaparib for frontline therapy and bev in the second line. And to your point, I think it’s our duty to at least consider both agents or classes of agents for every patient, so that they can get the benefit.

Krishnansu S. Tewari, MD: Absolutely.

Transcript Edited for Clarity

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Transcript:

Bradley Monk, MD, FACOG, FACS: So, Tom, there was a meta-analysis here addressing this concept of bevacizumab or PARP. I kind of like that. I know you read that and tell me what that showed.

Thomas Herzog, MD: Yeah, Brad, it was one of the papers that really caught my eye. It’s a little clever and I don’t know enough about the statistical means that were used. They used a SUCRA tool, which is to rank effect size with the surface under the cumulative ranking value that was applied. And I don’t know what that means exactly, so don’t pin me down on that. But the numbers look great. The bottom line is how do we interpret these 5 trials, right? How do we put those into practice and when do we use a PARP [poly ADP ribose polymerase] inhibitor, and when do we use bev [bevacizumab]? I think everyone on the panel, if you don’t agree, please speak up. But I think we all say that patients that are candidates for maintenance should be offered maintenance.

Bradley Monk, MD, FACOG, FACS: Yeah.

Thomas Herzog, MD: I think everyone agrees on that but what maintenance and how do we look at that. And what they tried to do is model from the 8 major trials that are out there and calculate a hazard ratio. And what they did is they looked at patients that were all-comers. And you might imagine you’re going to have a mix then of wild-type and mutations that are probably 20% or so mutations and 70%  not. But what’s more informative to me was the breakdown of the wild-type versus the BRCA-mutant. And what they did is they compared PARP versus bev, they compared PARP versus just chemo [chemotherapy] alone, or bev versus chemo alone. And for the BRCA-mutated patients, imagine of course who was going to win, it was obviously the PARP. So the PARP had 0.46 versus chemo hazard ratio is 0.25 which we already know. And bev?  also did well, hazard ratio of 0.55. Those are in the patients but not as well as the PARP in the BRCA-mutated patients.

And the wild-type saw a little bit of a diminution favoring the PARP, but it crossed 1 and it was 0.87. That’s the area that we don’t know, and that’s the biggest patient population that we have. And it still doesn’t completely decide that. But I was surprised to see it perform as well as it did. The PARP did quite well there. PARP did much better as did bev versus traditional chemo.

Bradley Monk, MD, FACOG, FACS: But this all fits now.

Thomas Herzog, MD: Yes.

Bradley Monk, MD, FACOG, FACS: So we said that probably most patients should get bev in frontline therapy, and if you got bev in the frontline, when you have a platinum-sensitive relapse, which almost all patients do, because you got bev and it extends the platinum-free interval, then you should get PARP inhibitor in the second line.

Thomas Herzog, MD: Yeah.

Bradley Monk, MD, FACOG, FACS: So that meta-analysis supports I think what we’re doing—bev for frontline therapy, PARP inhibitor second-line maintenance unless you’re BRCA-mutated, then you get olaparib for frontline therapy and bev in the second line. And to your point, I think it’s our duty to at least consider both agents or classes of agents for every patient, so that they can get the benefit.

Krishnansu S. Tewari, MD: Absolutely.

Transcript Edited for Clarity
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