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Ovarian Cancer: Deciding Among PARP Inhibitors

Insights From: Angeles Alvarez Secord, MD, Duke University Medical Center; Michelle Berke
Published: Wednesday, Jan 17, 2018



Transcript: 

Angeles Alvarez Secord, MD: So, Michelle we were talking about some of the exciting new drugs that are available in ovarian cancer, and you’re on a PARP inhibitor. And I want to share some of the decisions that we went through in terms of deciding on a PARP inhibitor, when and which one. And so, I want to go back to when you finished your second-line treatment of chemotherapy. You were on the bevacizumab and we did maintenance bevacizumab. That was actually a while ago, and I don’t know if you realized this at the time but none of the PARP inhibitors had been approved for maintenance yet. So, it wasn’t even an option that came up for us then.

Michelle Berke: I remember that. I think it came out December 2016.

Angeles Alvarez Secord, MD: So, now it is an option and if we were to go back in time, would our decisions be different?

Michelle Berke: That’s a good question.

Angeles Alvarez Secord, MD: It’s hard to know.

Michelle Berke: Yes, I’m just glad that it came out when it did.

Angeles Alvarez Secord, MD: Right. So, right now, there are 2 PARP inhibitors that are approved in the maintenance situation. Those are olaparib and niraparib. And the approval for those PARP inhibitors in that maintenance situation was we had platinum-sensitive chemotherapy and they responded to their chemotherapy with either a complete response or a partial response. It’s for all-comers. So, you don’t have to have the mutation.

Michelle Berke: Oh, interesting, OK.

Angeles Alvarez Secord, MD: You had a BRCA1 germline mutation, right? So, in this situation, any patient who is platinum sensitive who responds to that chemotherapy can go on a PARP inhibitor for maintenance treatment. And in somebody who has had a BRCA1 or BRCA2 mutation, either a germline mutation like you do or a mutation just in a tumor, the benefits in terms of disease control are pretty outstanding. We’re talking not just twice as long but almost 3 times, 4 times long.

Michelle Berke: Really?

Angeles Alvarez Secord, MD: Yes, that’s pretty dramatic. I’d give you the numbers, it doesn’t even really pop out in terms of the improvement on the curves that we’re talking 19 versus 5 months, 16 versus 5 months. I mean it’s…

Michelle Berke: A huge difference.

Angeles Alvarez Secord, MD: A huge difference, right. And there are some differences in terms of how you assess that data. But bottom line is it works, right? If somebody doesn’t have one of those mutations, but let’s say they have another mutation that’s associated with homologous recombination defects, there’s still a benefit. It’s not quite as strong but I think it was a 6- to 9-month benefit in those situations. And, again, you have to take these numbers with the grain of salt. The bottom line though is that it does work in that situation. And then if somebody doesn’t have indication at all, the benefit is less. It’s about a 3-month disease control. But you have to be careful with the numbers because one of the other things they talk about is hazard ratio. So, you’re basically decreasing the risk of disease coming back by, in some cases, 40% if somebody doesn’t have the mutation or the homologous recombination defect. I gave you a lot of information.

Michelle Berke: Yes.

Angeles Alvarez Secord, MD: But as a patient, what do you think of when somebody tells you all that?

Michelle Berke: As a patient, you go by statistics a lot because you want the best treatment that you can possibly get. So, if statistics are looking good in my favor, then that’s what I base my decisions on.

Angeles Alvarez Secord, MD: And with the BRCA1 mutation, it would look really good to get one of these drugs. So, they weren’t available for you at the time. We did bevacizumab, which I think makes a lot of sense given the data. You progressed, and at that point, we did talk about the fact that there was a drug available now called rucaparib. That’s a different PARP inhibitor. Rucaparib is one of the PARP inhibitors that has been approved for treatment, alright?

Michelle Berke: OK.

Angeles Alvarez Secord, MD: The other PARP inhibitor that’s approved for treatment is olaparib. So, I just want to go over this again because it’s very confusing.

Michelle Berke: It is very confusing.

Angeles Alvarez Secord, MD: There are 3 PARP inhibitors. They have different indications from the Food and Drug Administration about when you can use them and in which patient you can use them. Almost like I need a big table here.

Michelle Berke: Yes, just to show it up.

Angeles Alvarez Secord, MD: But just to go through them again, the maintenance indications are for niraparib and olaparib and the treatment indications are for olaparib for patients who have a germline mutation only.

Michelle Berke: Like me.

Angeles Alvarez Secord, MD: Yes, like you. And have had at least 3 prior chemotherapies. And then the other one is rucaparib, and that’s for patients who either have a germline mutation or somatic mutation. That means a mutation just in the tumor. They didn’t inherit it from a parent but they have a de novo mutation in the tumor, and have had 2 prior chemotherapies. So, actually, you can use rucaparib sooner than you can use olaparib. I think at some point these distinctions are just going to be a wash and all these PARP inhibitors are going to be approved across the board.

Michelle Berke: Oh good. We need it.

Angeles Alvarez Secord, MD: But right now, how we make those decisions is really based on the indication, the tumor, and the genetic germline mutation biomarker. So, it’s really important that patients have the conversation with the physician about which one of the PARP inhibitors, if any, they can get. And that’s one part of the treatment decision, right? And then the other part is a side effect profile. So, in your situation, we had rucaparib as an option. And we went for it.

Michelle Berke: It actually came out and was available right when I needed it.

Angeles Alvarez Secord, MD: Perfect timing.

Michelle Berke: Very perfect timing.

Angeles Alvarez Secord, MD: And what has your experience been on rucaparib so far?

Michelle Berke: The side effects have been minimal. I have drainage in my eyes and my nose, abdominal cramping once in a while. Fatigue is still there and that’s pretty much about it. I’m doing really well on it. Sometimes I get nauseous and I can’t eat but…

Angeles Alvarez Secord, MD: I remember one time asking you, how do you feel on the drugs compared to everything you’ve gotten in this whole experience?

Michelle Berke: It’s the best I’ve felt in over 4 years. My quality of life is really good right now.

Angeles Alvarez Secord, MD: And that really struck me because it was the best you felt in 4 years, so that included that time that you came off of any treatment and you were in your first remission. This is the best you felt.

Michelle Berke: This is the best, even when I was in remission for 6 months. That’s how well this drug is working with me.

Angeles Alvarez Secord, MD: Right. And I think that for some patients, these drugs could potentially represent a cure for someone with platinum-resistant, or platinum-sensitive, recurrent ovarian cancer. They’ve had some patients on these drugs long term, and in one of the studies, Study 19, which is an olaparib study, they have data going out 5 years, and there are a few patients that are long-term survivors.

Michelle Berke: Oh my.

Angeles Alvarez Secord, MD: Survivors, very exciting. You’re doing great.

Michelle Berke: That’s really good news.

Angeles Alvarez Secord, MD: Michelle, going to back to when we talked about starting on a PARP inhibitor, we knew that option was potentially coming months before it was even available. And I know your daughter even knew it was coming.

Michelle Berke: I know. She works for a clinical trial company.

Angeles Alvarez Secord, MD: She’s very smart and she was very interested in PARP inhibitors for you. But not everybody knows about these drugs, right? Maybe some of our patients don’t know about them. Maybe some of their doctors don’t know about them either. I personally think the PARP inhibitors and their approval in ovarian cancer is the most exciting thing we’ve had happen in years and years.

Michelle Berke: I agree.

Angeles Alvarez Secord, MD: It’s transformative.

Transcript Edited for Clarity 
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Transcript: 

Angeles Alvarez Secord, MD: So, Michelle we were talking about some of the exciting new drugs that are available in ovarian cancer, and you’re on a PARP inhibitor. And I want to share some of the decisions that we went through in terms of deciding on a PARP inhibitor, when and which one. And so, I want to go back to when you finished your second-line treatment of chemotherapy. You were on the bevacizumab and we did maintenance bevacizumab. That was actually a while ago, and I don’t know if you realized this at the time but none of the PARP inhibitors had been approved for maintenance yet. So, it wasn’t even an option that came up for us then.

Michelle Berke: I remember that. I think it came out December 2016.

Angeles Alvarez Secord, MD: So, now it is an option and if we were to go back in time, would our decisions be different?

Michelle Berke: That’s a good question.

Angeles Alvarez Secord, MD: It’s hard to know.

Michelle Berke: Yes, I’m just glad that it came out when it did.

Angeles Alvarez Secord, MD: Right. So, right now, there are 2 PARP inhibitors that are approved in the maintenance situation. Those are olaparib and niraparib. And the approval for those PARP inhibitors in that maintenance situation was we had platinum-sensitive chemotherapy and they responded to their chemotherapy with either a complete response or a partial response. It’s for all-comers. So, you don’t have to have the mutation.

Michelle Berke: Oh, interesting, OK.

Angeles Alvarez Secord, MD: You had a BRCA1 germline mutation, right? So, in this situation, any patient who is platinum sensitive who responds to that chemotherapy can go on a PARP inhibitor for maintenance treatment. And in somebody who has had a BRCA1 or BRCA2 mutation, either a germline mutation like you do or a mutation just in a tumor, the benefits in terms of disease control are pretty outstanding. We’re talking not just twice as long but almost 3 times, 4 times long.

Michelle Berke: Really?

Angeles Alvarez Secord, MD: Yes, that’s pretty dramatic. I’d give you the numbers, it doesn’t even really pop out in terms of the improvement on the curves that we’re talking 19 versus 5 months, 16 versus 5 months. I mean it’s…

Michelle Berke: A huge difference.

Angeles Alvarez Secord, MD: A huge difference, right. And there are some differences in terms of how you assess that data. But bottom line is it works, right? If somebody doesn’t have one of those mutations, but let’s say they have another mutation that’s associated with homologous recombination defects, there’s still a benefit. It’s not quite as strong but I think it was a 6- to 9-month benefit in those situations. And, again, you have to take these numbers with the grain of salt. The bottom line though is that it does work in that situation. And then if somebody doesn’t have indication at all, the benefit is less. It’s about a 3-month disease control. But you have to be careful with the numbers because one of the other things they talk about is hazard ratio. So, you’re basically decreasing the risk of disease coming back by, in some cases, 40% if somebody doesn’t have the mutation or the homologous recombination defect. I gave you a lot of information.

Michelle Berke: Yes.

Angeles Alvarez Secord, MD: But as a patient, what do you think of when somebody tells you all that?

Michelle Berke: As a patient, you go by statistics a lot because you want the best treatment that you can possibly get. So, if statistics are looking good in my favor, then that’s what I base my decisions on.

Angeles Alvarez Secord, MD: And with the BRCA1 mutation, it would look really good to get one of these drugs. So, they weren’t available for you at the time. We did bevacizumab, which I think makes a lot of sense given the data. You progressed, and at that point, we did talk about the fact that there was a drug available now called rucaparib. That’s a different PARP inhibitor. Rucaparib is one of the PARP inhibitors that has been approved for treatment, alright?

Michelle Berke: OK.

Angeles Alvarez Secord, MD: The other PARP inhibitor that’s approved for treatment is olaparib. So, I just want to go over this again because it’s very confusing.

Michelle Berke: It is very confusing.

Angeles Alvarez Secord, MD: There are 3 PARP inhibitors. They have different indications from the Food and Drug Administration about when you can use them and in which patient you can use them. Almost like I need a big table here.

Michelle Berke: Yes, just to show it up.

Angeles Alvarez Secord, MD: But just to go through them again, the maintenance indications are for niraparib and olaparib and the treatment indications are for olaparib for patients who have a germline mutation only.

Michelle Berke: Like me.

Angeles Alvarez Secord, MD: Yes, like you. And have had at least 3 prior chemotherapies. And then the other one is rucaparib, and that’s for patients who either have a germline mutation or somatic mutation. That means a mutation just in the tumor. They didn’t inherit it from a parent but they have a de novo mutation in the tumor, and have had 2 prior chemotherapies. So, actually, you can use rucaparib sooner than you can use olaparib. I think at some point these distinctions are just going to be a wash and all these PARP inhibitors are going to be approved across the board.

Michelle Berke: Oh good. We need it.

Angeles Alvarez Secord, MD: But right now, how we make those decisions is really based on the indication, the tumor, and the genetic germline mutation biomarker. So, it’s really important that patients have the conversation with the physician about which one of the PARP inhibitors, if any, they can get. And that’s one part of the treatment decision, right? And then the other part is a side effect profile. So, in your situation, we had rucaparib as an option. And we went for it.

Michelle Berke: It actually came out and was available right when I needed it.

Angeles Alvarez Secord, MD: Perfect timing.

Michelle Berke: Very perfect timing.

Angeles Alvarez Secord, MD: And what has your experience been on rucaparib so far?

Michelle Berke: The side effects have been minimal. I have drainage in my eyes and my nose, abdominal cramping once in a while. Fatigue is still there and that’s pretty much about it. I’m doing really well on it. Sometimes I get nauseous and I can’t eat but…

Angeles Alvarez Secord, MD: I remember one time asking you, how do you feel on the drugs compared to everything you’ve gotten in this whole experience?

Michelle Berke: It’s the best I’ve felt in over 4 years. My quality of life is really good right now.

Angeles Alvarez Secord, MD: And that really struck me because it was the best you felt in 4 years, so that included that time that you came off of any treatment and you were in your first remission. This is the best you felt.

Michelle Berke: This is the best, even when I was in remission for 6 months. That’s how well this drug is working with me.

Angeles Alvarez Secord, MD: Right. And I think that for some patients, these drugs could potentially represent a cure for someone with platinum-resistant, or platinum-sensitive, recurrent ovarian cancer. They’ve had some patients on these drugs long term, and in one of the studies, Study 19, which is an olaparib study, they have data going out 5 years, and there are a few patients that are long-term survivors.

Michelle Berke: Oh my.

Angeles Alvarez Secord, MD: Survivors, very exciting. You’re doing great.

Michelle Berke: That’s really good news.

Angeles Alvarez Secord, MD: Michelle, going to back to when we talked about starting on a PARP inhibitor, we knew that option was potentially coming months before it was even available. And I know your daughter even knew it was coming.

Michelle Berke: I know. She works for a clinical trial company.

Angeles Alvarez Secord, MD: She’s very smart and she was very interested in PARP inhibitors for you. But not everybody knows about these drugs, right? Maybe some of our patients don’t know about them. Maybe some of their doctors don’t know about them either. I personally think the PARP inhibitors and their approval in ovarian cancer is the most exciting thing we’ve had happen in years and years.

Michelle Berke: I agree.

Angeles Alvarez Secord, MD: It’s transformative.

Transcript Edited for Clarity 
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