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Evolving Role of PARP Inhibitors in Ovarian Cancer

Insights From: Angeles Alvarez Secord, MD, Duke University Medical Center; Michelle Berke
Published: Tuesday, Jan 23, 2018



Transcript: 


Angeles Alvarez Secord, MD: In our brief conversation, we’re talking mostly about your experience in treatment decisions for you and how you’re using a PARP inhibitor for the treatment of recurring ovarian cancer. But the other exciting part about these drugs is that many of them are being evaluated in the frontline setting. So, we can even move these up.

Michelle Berke: Oh, that’s really good news.

Angeles Alvarez Secord, MD: Right. So, one of the things you told me is that this is the best you’ve ever felt in 4 years. Can you imagine, at some point in your life, being able to bypass some of those chemotherapies and just jump right to a PARP inhibitor?

Michelle Berke: Just jump to a PARP inhibitor? That would have been great if I was able to do that.

Angeles Alvarez Secord, MD: There’s a variety of combinations being evaluated. When you recurred, these studies weren’t available but there’s at least 2 studies that I know of that are evaluating olaparib in combination with other therapies in large clinical trials. And they’re comparing them to standard of care chemotherapy. And so, in both of these studies, it’s olaparib plus cediranib. Cediranib is like bevacizumab but a little bit different. 

Michelle Berke: OK.

Angeles Alvarez Secord, MD: It’s an antiangiogenic agent, but it’s a tyrosine kinase inhibitor. It has a little different side effect profile than bevacizumab, but when they combined these drugs together, they showed this tremendous improvement in disease control, specifically in women who didn’t have the mutation. So, if you have a mutation, who knows, it may be that the PARP inhibitors are enough. But if you don’t have a mutation, by adding it with these other drugs, you can harness more of the PARP inhibitor activity or synergistic way that it works with the other drug you’re adding. So, that’s one combination they’re evaluating now. And the results of those studies may change when and how we can use these drugs sooner.

There are studies of the other PARP inhibitors in combination with either antiangiogenic agents or with immunotherapy agents. So, immunotherapy agents we haven’t talked about too much. But these are immuno-oncology drugs. The most common drugs being used right now are checkpoint inhibitors.

Your immune system’s trying to fight the cancer, but the cancer’s finding ways to hide from it. And one of the ways that it does is actually tricking the immune cells into not recognizing them.

Michelle Berke: Great.

Angeles Alvarez Secord, MD: So, some of these new drugs, called checkpoint inhibitors, prevent the tumor cell from doing that and really harness your own immune system to work with it. Some say that if you add a PARP inhibitor with an immune therapy, you can have a synergistic effect. There are a lot of details diving into the science about how that happens. So, that’s also on the forefront.

And then, who knows, at some point we may find that we have an indication for PARP inhibitor maintenance in the frontline setting. SOLO-1 is a trial that’s being completed in the frontline setting, and there are other studies that are currently underway. So, a lot of exciting opportunities in the future, either moving PARPs up or adding PARP inhibitors to other drugs so that you can get that benefit for all patients with ovarian cancer.

Transcript Edited for Clarity 
 
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Transcript: 


Angeles Alvarez Secord, MD: In our brief conversation, we’re talking mostly about your experience in treatment decisions for you and how you’re using a PARP inhibitor for the treatment of recurring ovarian cancer. But the other exciting part about these drugs is that many of them are being evaluated in the frontline setting. So, we can even move these up.

Michelle Berke: Oh, that’s really good news.

Angeles Alvarez Secord, MD: Right. So, one of the things you told me is that this is the best you’ve ever felt in 4 years. Can you imagine, at some point in your life, being able to bypass some of those chemotherapies and just jump right to a PARP inhibitor?

Michelle Berke: Just jump to a PARP inhibitor? That would have been great if I was able to do that.

Angeles Alvarez Secord, MD: There’s a variety of combinations being evaluated. When you recurred, these studies weren’t available but there’s at least 2 studies that I know of that are evaluating olaparib in combination with other therapies in large clinical trials. And they’re comparing them to standard of care chemotherapy. And so, in both of these studies, it’s olaparib plus cediranib. Cediranib is like bevacizumab but a little bit different. 

Michelle Berke: OK.

Angeles Alvarez Secord, MD: It’s an antiangiogenic agent, but it’s a tyrosine kinase inhibitor. It has a little different side effect profile than bevacizumab, but when they combined these drugs together, they showed this tremendous improvement in disease control, specifically in women who didn’t have the mutation. So, if you have a mutation, who knows, it may be that the PARP inhibitors are enough. But if you don’t have a mutation, by adding it with these other drugs, you can harness more of the PARP inhibitor activity or synergistic way that it works with the other drug you’re adding. So, that’s one combination they’re evaluating now. And the results of those studies may change when and how we can use these drugs sooner.

There are studies of the other PARP inhibitors in combination with either antiangiogenic agents or with immunotherapy agents. So, immunotherapy agents we haven’t talked about too much. But these are immuno-oncology drugs. The most common drugs being used right now are checkpoint inhibitors.

Your immune system’s trying to fight the cancer, but the cancer’s finding ways to hide from it. And one of the ways that it does is actually tricking the immune cells into not recognizing them.

Michelle Berke: Great.

Angeles Alvarez Secord, MD: So, some of these new drugs, called checkpoint inhibitors, prevent the tumor cell from doing that and really harness your own immune system to work with it. Some say that if you add a PARP inhibitor with an immune therapy, you can have a synergistic effect. There are a lot of details diving into the science about how that happens. So, that’s also on the forefront.

And then, who knows, at some point we may find that we have an indication for PARP inhibitor maintenance in the frontline setting. SOLO-1 is a trial that’s being completed in the frontline setting, and there are other studies that are currently underway. So, a lot of exciting opportunities in the future, either moving PARPs up or adding PARP inhibitors to other drugs so that you can get that benefit for all patients with ovarian cancer.

Transcript Edited for Clarity 
 
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