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PARP Combination Therapies in Ovarian Cancer

Panelists: Bradley J. Monk, MD, FACS, FACOG, Arizona Oncology Practice of US Oncology; Oliver Dorigo, MD, PhD, Stanford University Medical Center; Thomas Herzog, MD, University of Cincinnati Cancer Institute; Kathleen Moore, MD, Stephenson Cancer Center; Leslie M. Randall, MD, MAS, University of California, Irvine
Published: Thursday, Sep 20, 2018



Transcript: 

Bradley J. Monk, MD, FACS, FACOG: We want more, and we want to combine things. Leslie, I know one of the things that you’re passionate about is adding checkpoint inhibitors to PARP inhibitors. There’s a study called TOPACIO. Can you tell us about TOPACIO?

Leslie M. Randall, MD, MAS: Yes. TOPACIO takes this to the next level. This is PARP inhibitor in addition to pembrolizumab, a PD-1 inhibitor. The PARP inhibitor is niraparib. At the current time, they’re looking at both breast cancer patients and platinum-resistant recurrent ovarian cancer patients.

TOPACIO was presented at the 2018 Society for Gynecologic Oncology Annual Meeting. The combination does, in fact, work. And interestingly, there was a signal not only in the biomarker-positive groups, in adding your PD-L1 biomarker to that molecular signature with HRD, but there was also a signal in those who were biomarker-negative.

Bradley J. Monk, MD, FACS, FACOG: What’s the response rate?

Leslie M. Randall, MD, MAS: The overall response rate is about 12% to 20%, but this needs to be further studied, especially in ovarian cancer.

Bradley J. Monk, MD, FACS, FACOG: The study is ongoing.

Leslie M. Randall, MD, MAS: The study is ongoing, and this needs to be expanded to have a larger ovarian cancer cohort. But, it’s certainly worthy of further study.

Bradley J. Monk, MD, FACS, FACOG: Here’s what people say, and I know that you’re going to jump on me. In the MEDIOLA trial, which is olaparib/durvalumab, the rate is 70%. When you tell me that this is 20% to 25%, that’s half.

Leslie M. Randall, MD, MAS: I think you have to look at the differences in the populations. MEDIOLA looked at a platinum-sensitive population. We’ve been talking about how our PARP inhibitors are effective in these patients. With the addition of durvalumab, I’m not sure.

Bradley J. Monk, MD, FACS, FACOG: In a biomarker-positive group.

Leslie M. Randall, MD, MAS: Exactly. TOPACIO is a completely different approach in the resistant population, which is an unmet medical need.

Bradley J. Monk, MD, FACS, FACOG: Tom, I know you’re passionate about adding PARP inhibitors with an antiangiogenic. She says to use PARP with immuno-oncology. Maybe we can combine a PARP and antiangiogenic? What do you think?

Thomas Herzog, MD: I think it’s interesting. There’s preclinical data in all of these areas with these combinations of PARP inhibitors with antiangiogenics and PARP inhibitors with I-O therapies. The I-O story is interesting. You may change the sensitivity by creating these neoantigens, increasing the mutational load, and then coming in and hitting it with the I-O. There’s a study known as ANANOVA that’s looking at a PARP inhibitor with niraparib plus or minus bevacizumab. It’s a phase I, phase II program. We should have data early next year. It’s really an interesting strategy. You’re basically sparing the patient of platinum in a platinum-sensitive setting, which is really an interesting strategy. And, frankly, the response rates and the duration of responses that we’re seeing make it a strategy that should be looked at.

Bradley J. Monk, MD, FACS, FACOG: And that’s being expanded in the OVARIO study, right?

Thomas Herzog, MD: Right. OVARIO is niraparib and plus or minus bevacizumab in the platinum-sensitive maintenance setting.

Bradley J. Monk, MD, FACS, FACOG: That’s great.

Transcript Edited for Clarity 

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Transcript: 

Bradley J. Monk, MD, FACS, FACOG: We want more, and we want to combine things. Leslie, I know one of the things that you’re passionate about is adding checkpoint inhibitors to PARP inhibitors. There’s a study called TOPACIO. Can you tell us about TOPACIO?

Leslie M. Randall, MD, MAS: Yes. TOPACIO takes this to the next level. This is PARP inhibitor in addition to pembrolizumab, a PD-1 inhibitor. The PARP inhibitor is niraparib. At the current time, they’re looking at both breast cancer patients and platinum-resistant recurrent ovarian cancer patients.

TOPACIO was presented at the 2018 Society for Gynecologic Oncology Annual Meeting. The combination does, in fact, work. And interestingly, there was a signal not only in the biomarker-positive groups, in adding your PD-L1 biomarker to that molecular signature with HRD, but there was also a signal in those who were biomarker-negative.

Bradley J. Monk, MD, FACS, FACOG: What’s the response rate?

Leslie M. Randall, MD, MAS: The overall response rate is about 12% to 20%, but this needs to be further studied, especially in ovarian cancer.

Bradley J. Monk, MD, FACS, FACOG: The study is ongoing.

Leslie M. Randall, MD, MAS: The study is ongoing, and this needs to be expanded to have a larger ovarian cancer cohort. But, it’s certainly worthy of further study.

Bradley J. Monk, MD, FACS, FACOG: Here’s what people say, and I know that you’re going to jump on me. In the MEDIOLA trial, which is olaparib/durvalumab, the rate is 70%. When you tell me that this is 20% to 25%, that’s half.

Leslie M. Randall, MD, MAS: I think you have to look at the differences in the populations. MEDIOLA looked at a platinum-sensitive population. We’ve been talking about how our PARP inhibitors are effective in these patients. With the addition of durvalumab, I’m not sure.

Bradley J. Monk, MD, FACS, FACOG: In a biomarker-positive group.

Leslie M. Randall, MD, MAS: Exactly. TOPACIO is a completely different approach in the resistant population, which is an unmet medical need.

Bradley J. Monk, MD, FACS, FACOG: Tom, I know you’re passionate about adding PARP inhibitors with an antiangiogenic. She says to use PARP with immuno-oncology. Maybe we can combine a PARP and antiangiogenic? What do you think?

Thomas Herzog, MD: I think it’s interesting. There’s preclinical data in all of these areas with these combinations of PARP inhibitors with antiangiogenics and PARP inhibitors with I-O therapies. The I-O story is interesting. You may change the sensitivity by creating these neoantigens, increasing the mutational load, and then coming in and hitting it with the I-O. There’s a study known as ANANOVA that’s looking at a PARP inhibitor with niraparib plus or minus bevacizumab. It’s a phase I, phase II program. We should have data early next year. It’s really an interesting strategy. You’re basically sparing the patient of platinum in a platinum-sensitive setting, which is really an interesting strategy. And, frankly, the response rates and the duration of responses that we’re seeing make it a strategy that should be looked at.

Bradley J. Monk, MD, FACS, FACOG: And that’s being expanded in the OVARIO study, right?

Thomas Herzog, MD: Right. OVARIO is niraparib and plus or minus bevacizumab in the platinum-sensitive maintenance setting.

Bradley J. Monk, MD, FACS, FACOG: That’s great.

Transcript Edited for Clarity 
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