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Novel Agents and the Future Treatment of Ovarian Cancer

Panelists: Bradley J. Monk, MD, FACS, FACOG, University of Arizona and Creighton University; Michael J. Birrer, MD, PhD The University of Alabama at Birmingham; Ursula A. Matulonis, MD, Harvard Medical School
Published: Thursday, Jan 03, 2019



Transcript:

Bradley J. Monk, MD:
So, the last thing we want to talk about is the olaparib, cediranib [maleate] trial. We’ve talked about immunotherapy and PARP [poly ADP ribose polymerase]. We’ve talked about immunotherapy and bevacizumab [Avastin]. We have not talked about PARP antiangiogenics. And olaparib and cediranib are made by the same pharmaceutical company. So, what about PARP and anti-VEGF [anti-vascular endothelial growth factor] together? So olaparib, cediranib.

Ursula A. Matulonis, MD: So PARP and antiangiogenic, I mean obviously that’s going to be something like PAOLA-1, but this is a different approach than using different intravascular drugs. Cediranib, which is an oral VEGF receptor 1, 2, and 3 inhibitor, has other targets as well. But this is a trial from a phase 1 standpoint started nearly 10 years ago and has evolved into 2 phase 3 trials testing this combination, which is very active but also has some important toxicities and comparing it to standard of care—platinum doublet for platinum sensitive recurrence in GY004, or in the platinum-resistant setting, testing this doublet against standard of care chemotherapy, such as [pegylated] liposomal doxorubicin or weekly paclitaxel. So GY004 is expecting results in 2019. And GY005 is ongoing. I think the other issues  are that the control groups in some of these trials, because it takes so long to do trials, [are] not always necessarily the standard of care.

Bradley J. Monk, MD: Well the control arms are better than a placebo though.

Ursula A. Matulonis, MD: That’s true, yes.

Bradley J. Monk, MD: I mean we just talked about SOLO-1 where the control arm was a placebo. So at least those control arms have a control arm.

Ursula A. Matulonis, MD: Absolutely, you’re correct. But it always involves a lot of discussion to really interpret the results and make it, those results, clinically translatable to patients.

Bradley J. Monk, MD: That’s right. So we’ve had a wonderful conversation about frontline and recurrent ovarian cancer. I’m going to give you each a second here for some closing remarks and then I’m going to finish. But I really enjoyed this encounter. Mike, give us your closing thoughts about this evolving paradigm in how treat epithelial ovarian cancer.

Michael J. Birrer, MD, PhD: Well, just a couple of comments, we sort of touched upon it. It’s the most exciting time I’ve had in oncology in 30 years. We have choices. It’s made the clinician actually more important because they have to interpret all of it and give the best opportunity for the patients. So that’s all very good. And then finally, because biomarkers have been my lifeblood, but you know it’s been tough in terms of finding the right biomarkers for the clinical needs. That’s become even more important now than it was 15 years ago. So sort of tailoring these therapies to our patients in a very scientifically sound way will require biomarkers that are very predictive. We’ve got our work cut out for us. It will be hopefully important.

Ursula A. Matulonis, MD: I just want to make 2 points and one is on Mike’s lines around just really the importance of the science involved, and how that does make our job pretty exciting and it really allows us to engage patients as well. You know, underlying histology that translates into different molecular profiles, understanding how the different drugs are going to work along these different clinical parameters, kind of genomic parameters. And then secondly is really understanding that clinical trials exist everywhere. I think it’s for patients treated in the community, after they’ve gone through platinum and liposomal doxorubicin, and topotecan, and gemcitabine, and then the [doctor] says, “Well you know what, I think we’ve run out of options.” That, to me, is unacceptable because if she’s got a good performance status, there are just loads of different trials out and around at our different centers where we’re testing really new strategies. And these strategies of PARP inhibitors and immunotherapy were the trials that we’ve been doing for the past 10 years. So patients, even if they’re heavily pretreated, can absolutely….

Bradley J. Monk, MD: Still have options.

Ursula A. Matulonis, MD: Still have options and they can respond to those options.

Bradley J. Monk, MD: So thank you all for your contributions to this discussion. On behalf of our panel, we thank you for joining us. We hope you found this OncLive Peer Exchange® to be useful and informative. I hope to see you again soon. So long for now.

Transcript Edited for Clarity.

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Transcript:

Bradley J. Monk, MD:
So, the last thing we want to talk about is the olaparib, cediranib [maleate] trial. We’ve talked about immunotherapy and PARP [poly ADP ribose polymerase]. We’ve talked about immunotherapy and bevacizumab [Avastin]. We have not talked about PARP antiangiogenics. And olaparib and cediranib are made by the same pharmaceutical company. So, what about PARP and anti-VEGF [anti-vascular endothelial growth factor] together? So olaparib, cediranib.

Ursula A. Matulonis, MD: So PARP and antiangiogenic, I mean obviously that’s going to be something like PAOLA-1, but this is a different approach than using different intravascular drugs. Cediranib, which is an oral VEGF receptor 1, 2, and 3 inhibitor, has other targets as well. But this is a trial from a phase 1 standpoint started nearly 10 years ago and has evolved into 2 phase 3 trials testing this combination, which is very active but also has some important toxicities and comparing it to standard of care—platinum doublet for platinum sensitive recurrence in GY004, or in the platinum-resistant setting, testing this doublet against standard of care chemotherapy, such as [pegylated] liposomal doxorubicin or weekly paclitaxel. So GY004 is expecting results in 2019. And GY005 is ongoing. I think the other issues  are that the control groups in some of these trials, because it takes so long to do trials, [are] not always necessarily the standard of care.

Bradley J. Monk, MD: Well the control arms are better than a placebo though.

Ursula A. Matulonis, MD: That’s true, yes.

Bradley J. Monk, MD: I mean we just talked about SOLO-1 where the control arm was a placebo. So at least those control arms have a control arm.

Ursula A. Matulonis, MD: Absolutely, you’re correct. But it always involves a lot of discussion to really interpret the results and make it, those results, clinically translatable to patients.

Bradley J. Monk, MD: That’s right. So we’ve had a wonderful conversation about frontline and recurrent ovarian cancer. I’m going to give you each a second here for some closing remarks and then I’m going to finish. But I really enjoyed this encounter. Mike, give us your closing thoughts about this evolving paradigm in how treat epithelial ovarian cancer.

Michael J. Birrer, MD, PhD: Well, just a couple of comments, we sort of touched upon it. It’s the most exciting time I’ve had in oncology in 30 years. We have choices. It’s made the clinician actually more important because they have to interpret all of it and give the best opportunity for the patients. So that’s all very good. And then finally, because biomarkers have been my lifeblood, but you know it’s been tough in terms of finding the right biomarkers for the clinical needs. That’s become even more important now than it was 15 years ago. So sort of tailoring these therapies to our patients in a very scientifically sound way will require biomarkers that are very predictive. We’ve got our work cut out for us. It will be hopefully important.

Ursula A. Matulonis, MD: I just want to make 2 points and one is on Mike’s lines around just really the importance of the science involved, and how that does make our job pretty exciting and it really allows us to engage patients as well. You know, underlying histology that translates into different molecular profiles, understanding how the different drugs are going to work along these different clinical parameters, kind of genomic parameters. And then secondly is really understanding that clinical trials exist everywhere. I think it’s for patients treated in the community, after they’ve gone through platinum and liposomal doxorubicin, and topotecan, and gemcitabine, and then the [doctor] says, “Well you know what, I think we’ve run out of options.” That, to me, is unacceptable because if she’s got a good performance status, there are just loads of different trials out and around at our different centers where we’re testing really new strategies. And these strategies of PARP inhibitors and immunotherapy were the trials that we’ve been doing for the past 10 years. So patients, even if they’re heavily pretreated, can absolutely….

Bradley J. Monk, MD: Still have options.

Ursula A. Matulonis, MD: Still have options and they can respond to those options.

Bradley J. Monk, MD: So thank you all for your contributions to this discussion. On behalf of our panel, we thank you for joining us. We hope you found this OncLive Peer Exchange® to be useful and informative. I hope to see you again soon. So long for now.

Transcript Edited for Clarity.
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