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Distinguishing Between PARP Inhibitors in Breast Cancer

Panelists:Joyce OShaugnessy, MD, Baylor University Medical Center; Tiffany A. Traina, MD, Memorial Sloan Kettering Cancer Center; Nadine M. Tung, MD, Harvard Medical School
Published: Wednesday, Apr 25, 2018



Transcript: 

Joyce O’Shaughnessy, MD: It sounds like the efficacy data were very similar between talazoparib and olaparib. They were very, very similar in that sort of later-line population. There were some differences in toxicities, but they were not wildly dramatic. So it sounds like they may not be totally interchangeable.

Tiffany Traina, MD: Right. I think that it’s really a bit of a toxicity differentiator. You already mentioned the alopecia standpoint. I think it was incredibly uncommon—maybe 2% or so in OlympiAD versus 25% in EMBRACA. Alopecia is meaningful if we’re trying to get away from significant toxicity for our patients. A bit more of hematologic toxicity was seen in EMBRACA with a PARP inhibitor versus olaparib on OlympiAD. In EMBRACA, I think they called out a subset of patients who had prior stable CNS [central nervous system] metastases, and it appeared that they derived a benefit. I don’t think that tells us that olaparib wouldn’t have benefit in that situation, but we just don’t see any differential response in the setting of CNS disease.

Nadine Tung, MD: I agree. There have been a lot of points made regarding the different PARP inhibitors, their mechanisms of action, the trapping of PARP proteins, and being more potent or less potent. We see tables about which ones are more potent. But with these 2 drugs, it looks like the efficacy, thus far, is pretty similar. So I don’t know whether any of that potency or mechanism of action is going to translate to clinical differences or toxicity differences. We don’t know.

Joyce O’Shaughnessy, MD: We don’t know yet. That’s the trapping of the PARP enzyme, so it doesn’t fall off. You really just don’t complete that repair of double-strand breaks. We just don’t know yet. That’s a potency issue, but we don’t know yet, clinically. There was more anemia, neutropenia, and thrombocytopenia. Is that right?

Nadine Tung, MD: Absolutely. If you look at how much grade 3 or higher anemia there was, with olaparib (in OlympiAD), the number was 16%. The number was like 40% in the EMBRACA study with talazoparib.
If you look at thrombocytopenia (grade 3 or higher), you’re talking about 2% versus 15%. So there are differences. No doubt, when you look at the studies, one thinks, Well, is one of these more potent? Is one more toxic? But, again, does that translate into efficacy? Will it translate into survival? I think time will tell. At this point, the efficacy looks similar.

Joyce O’Shaughnessy, MD: There was a difference in BRCA1 and BRCA2, between the studies, I think. Wasn’t there a little suggestion that talazoparib looked quite good in the BRCA2 setting? And then, in the OlympiAD trial, maybe that wasn’t quite as prominent or something?

Tiffany Traina, MD: OlympiAD is a 60/40 split—60% in BRCA1 and 40% in BRCA2—and 50/50 for ER-positive and triple-negative.

Nadine Tung, MD: And so, again, I think when you look at these forest plots, at this point, I can’t find a subgroup of patients who met the eligibility criteria that I wouldn’t use either olaparib or….

Joyce O’Shaughnessy, MD: Because we’re getting into subset analyses.

Nadine Tung, MD: Which were not planned. They’re exploratory.

Joyce O’Shaughnessy, MD: And the confidence intervals are fully overlapping.

Nadine Tung, MD: Absolutely.

Joyce O’Shaughnessy, MD: That is something that I remember having a question on. But yes, these are subset analyses. It’s like the CDK4/6 inhibitors—every single subset benefits.

Transcript Edited for Clarity 
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Transcript: 

Joyce O’Shaughnessy, MD: It sounds like the efficacy data were very similar between talazoparib and olaparib. They were very, very similar in that sort of later-line population. There were some differences in toxicities, but they were not wildly dramatic. So it sounds like they may not be totally interchangeable.

Tiffany Traina, MD: Right. I think that it’s really a bit of a toxicity differentiator. You already mentioned the alopecia standpoint. I think it was incredibly uncommon—maybe 2% or so in OlympiAD versus 25% in EMBRACA. Alopecia is meaningful if we’re trying to get away from significant toxicity for our patients. A bit more of hematologic toxicity was seen in EMBRACA with a PARP inhibitor versus olaparib on OlympiAD. In EMBRACA, I think they called out a subset of patients who had prior stable CNS [central nervous system] metastases, and it appeared that they derived a benefit. I don’t think that tells us that olaparib wouldn’t have benefit in that situation, but we just don’t see any differential response in the setting of CNS disease.

Nadine Tung, MD: I agree. There have been a lot of points made regarding the different PARP inhibitors, their mechanisms of action, the trapping of PARP proteins, and being more potent or less potent. We see tables about which ones are more potent. But with these 2 drugs, it looks like the efficacy, thus far, is pretty similar. So I don’t know whether any of that potency or mechanism of action is going to translate to clinical differences or toxicity differences. We don’t know.

Joyce O’Shaughnessy, MD: We don’t know yet. That’s the trapping of the PARP enzyme, so it doesn’t fall off. You really just don’t complete that repair of double-strand breaks. We just don’t know yet. That’s a potency issue, but we don’t know yet, clinically. There was more anemia, neutropenia, and thrombocytopenia. Is that right?

Nadine Tung, MD: Absolutely. If you look at how much grade 3 or higher anemia there was, with olaparib (in OlympiAD), the number was 16%. The number was like 40% in the EMBRACA study with talazoparib.
If you look at thrombocytopenia (grade 3 or higher), you’re talking about 2% versus 15%. So there are differences. No doubt, when you look at the studies, one thinks, Well, is one of these more potent? Is one more toxic? But, again, does that translate into efficacy? Will it translate into survival? I think time will tell. At this point, the efficacy looks similar.

Joyce O’Shaughnessy, MD: There was a difference in BRCA1 and BRCA2, between the studies, I think. Wasn’t there a little suggestion that talazoparib looked quite good in the BRCA2 setting? And then, in the OlympiAD trial, maybe that wasn’t quite as prominent or something?

Tiffany Traina, MD: OlympiAD is a 60/40 split—60% in BRCA1 and 40% in BRCA2—and 50/50 for ER-positive and triple-negative.

Nadine Tung, MD: And so, again, I think when you look at these forest plots, at this point, I can’t find a subgroup of patients who met the eligibility criteria that I wouldn’t use either olaparib or….

Joyce O’Shaughnessy, MD: Because we’re getting into subset analyses.

Nadine Tung, MD: Which were not planned. They’re exploratory.

Joyce O’Shaughnessy, MD: And the confidence intervals are fully overlapping.

Nadine Tung, MD: Absolutely.

Joyce O’Shaughnessy, MD: That is something that I remember having a question on. But yes, these are subset analyses. It’s like the CDK4/6 inhibitors—every single subset benefits.

Transcript Edited for Clarity 
View Conference Coverage
Online CME Activities
TitleExpiration DateCME Credits
34th Annual Miami Breast Cancer Conference® Clinical Case Vignette Series™May 25, 20182.0
Community Practice Connections™: CDK4/6 Inhibitors With the Experts: The Role of Emerging Agents for the Management of Metastatic Breast CancerMay 30, 20182.0
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