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PARP + Maintenance Bevacizumab in Ovarian Cancer

Panelists: Bradley J. Monk, MD, FACOG, FACS, University of Arizona; Creighton University School of Medicine; Arizona Oncology; Kathleen N. Moore, MD, University of Oklahoma; Elena S. Ratner, MD, Yale University School of Medicine; Brian M. Slomovitz, MD, Sylvester Comprehensive Cancer Center, University of Miami Health System
Published: Monday, May 20, 2019



Transcript: 

Bradley J. Monk, MD, FACOG, FACS: Before we move to recurrent disease, I want to talk about this idea of adding olaparib to GOG-0218 [Gynecologic Oncology Group Study 0218], or bevacizumab. That’s being tested, and that will be a report hopefully within the next year or so. Tell us about the study which you know as PAOLA-1.

Kathleen N. Moore, MD: This is an important study. It is a randomized study. It’s entirely done in Europe, where bevacizumab has been incorporated in the frontline maintenance setting in almost all countries for many years. It is the standard of care. All patients received platinum-taxane chemotherapy with bevacizumab. And then, at the time that they finish, if they are in complete or partial response, they’re randomized to continue bevacizumab maintenance plus placebo, or they get bevacizumab maintenance for 12 cycles, because that’s the standard in Europe, and 24 months of olaparib, just like in SOLO-1.

The primary endpoint is investigator-assessed progression-free survival. The stratification factor is BRCA patients, and there’s a fair number of BRCA patients. It’s not over enriched, but there’s a fair number of BRCA patients on that study. Now of course, this is pre–SOLO-1, so you wouldn’t randomize a BRCA patient to a nonolaparib arm anymore. But we’re going to have that data coming out. This is not really just a me-too sort of study. There is real preclinical and translational evidence that there’s synergy between PARP [poly (ADP-ribose) polymerase] inhibition and antiangiogenic agents through a number of mechanisms that lead to downregulation of DNA-repair proteins and an induction of kind of a BRCA-type of behavior that then will respond to a PARP inhibitor. So that’s going to be an important study, mainly, and it will be hard to tell. Honestly, if you ask me, I think it’s going to be positive. I don’t think they’re going to break out the subgroups.

Bradley J. Monk, MD, FACOG, FACS: They have to.

Kathleen N. Moore, MD: Well, they may not. But if they do, I’m most interested in the BRCA wild type because I think that’s really who’s going to benefit.

Bradley J. Monk, MD, FACOG, FACS: Absolutely.

Kathleen N. Moore, MD: It’s going to be hard to say.

Bradley J. Monk, MD, FACOG, FACS: Which is the majority of patients.

Kathleen N. Moore, MD: Which is the majority. It’s going to be hard to say, in a BRCA patient, whether or not the addition of bevacizumab adds anything over olaparib alone. So that’s going to be the unanswered question there.

Bradley J. Monk, MD, FACOG, FACS: Brian, if PAOLA-1 is positive, meaning that you add olaparib to the 15 months of bevacizumab to a level that’s acceptable for regulatory, and then based on the BOOST trial, which is 30 months of bevacizumab versus 15, are you going to stop the olaparib at 15 months and then continue bevacizumab for an additional 15 months? Or are you going to try to make a case for giving both for 30 months?

Kathleen N. Moore, MD: Well, the olaparib goes for 24 months.

Bradley J. Monk, MD, FACOG, FACS: OK.

Kathleen N. Moore, MD: Twenty-four cycles.

Bradley J. Monk, MD, FACOG, FACS: Twenty-four cycles. But still, the bevacizumab could go longer.

Kathleen N. Moore, MD: It could go longer.

Brian M. Slomovitz, MD: So just to highlight, what are we talking about here? We’re talking about 24 months, 30 months for ovarian cancer in the first line. These are things that we’ve never talked about before. How great is that?

Bradley J. Monk, MD, FACOG, FACS: How great is that? Thank you for that.

Brian M. Slomovitz, MD: So that qualifies the fact that I don’t know the right answer. I think if we could keep the olaparib, I think that’s the active drug. Keeping it on longer probably would make sense. But the BOOST trial—I’d be interested to see those results as well.

Transcript Edited for Clarity

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Transcript: 

Bradley J. Monk, MD, FACOG, FACS: Before we move to recurrent disease, I want to talk about this idea of adding olaparib to GOG-0218 [Gynecologic Oncology Group Study 0218], or bevacizumab. That’s being tested, and that will be a report hopefully within the next year or so. Tell us about the study which you know as PAOLA-1.

Kathleen N. Moore, MD: This is an important study. It is a randomized study. It’s entirely done in Europe, where bevacizumab has been incorporated in the frontline maintenance setting in almost all countries for many years. It is the standard of care. All patients received platinum-taxane chemotherapy with bevacizumab. And then, at the time that they finish, if they are in complete or partial response, they’re randomized to continue bevacizumab maintenance plus placebo, or they get bevacizumab maintenance for 12 cycles, because that’s the standard in Europe, and 24 months of olaparib, just like in SOLO-1.

The primary endpoint is investigator-assessed progression-free survival. The stratification factor is BRCA patients, and there’s a fair number of BRCA patients. It’s not over enriched, but there’s a fair number of BRCA patients on that study. Now of course, this is pre–SOLO-1, so you wouldn’t randomize a BRCA patient to a nonolaparib arm anymore. But we’re going to have that data coming out. This is not really just a me-too sort of study. There is real preclinical and translational evidence that there’s synergy between PARP [poly (ADP-ribose) polymerase] inhibition and antiangiogenic agents through a number of mechanisms that lead to downregulation of DNA-repair proteins and an induction of kind of a BRCA-type of behavior that then will respond to a PARP inhibitor. So that’s going to be an important study, mainly, and it will be hard to tell. Honestly, if you ask me, I think it’s going to be positive. I don’t think they’re going to break out the subgroups.

Bradley J. Monk, MD, FACOG, FACS: They have to.

Kathleen N. Moore, MD: Well, they may not. But if they do, I’m most interested in the BRCA wild type because I think that’s really who’s going to benefit.

Bradley J. Monk, MD, FACOG, FACS: Absolutely.

Kathleen N. Moore, MD: It’s going to be hard to say.

Bradley J. Monk, MD, FACOG, FACS: Which is the majority of patients.

Kathleen N. Moore, MD: Which is the majority. It’s going to be hard to say, in a BRCA patient, whether or not the addition of bevacizumab adds anything over olaparib alone. So that’s going to be the unanswered question there.

Bradley J. Monk, MD, FACOG, FACS: Brian, if PAOLA-1 is positive, meaning that you add olaparib to the 15 months of bevacizumab to a level that’s acceptable for regulatory, and then based on the BOOST trial, which is 30 months of bevacizumab versus 15, are you going to stop the olaparib at 15 months and then continue bevacizumab for an additional 15 months? Or are you going to try to make a case for giving both for 30 months?

Kathleen N. Moore, MD: Well, the olaparib goes for 24 months.

Bradley J. Monk, MD, FACOG, FACS: OK.

Kathleen N. Moore, MD: Twenty-four cycles.

Bradley J. Monk, MD, FACOG, FACS: Twenty-four cycles. But still, the bevacizumab could go longer.

Kathleen N. Moore, MD: It could go longer.

Brian M. Slomovitz, MD: So just to highlight, what are we talking about here? We’re talking about 24 months, 30 months for ovarian cancer in the first line. These are things that we’ve never talked about before. How great is that?

Bradley J. Monk, MD, FACOG, FACS: How great is that? Thank you for that.

Brian M. Slomovitz, MD: So that qualifies the fact that I don’t know the right answer. I think if we could keep the olaparib, I think that’s the active drug. Keeping it on longer probably would make sense. But the BOOST trial—I’d be interested to see those results as well.

Transcript Edited for Clarity
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