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Sequencing in BRCA-Positive TNBC Patients

Panelists: Aditya Bardia, MD, MPH, Massachusetts General Hospital Center; Claudine Isaacs, MD, Lombardi Comprehensive Cancer Center; Joyce O'Shaughnessy, MD, Baylor University Medical Center Texas Oncology; Tiffany Traina, MD, Memorial Sloan Kettering Cancer Center
Published: Friday, Mar 02, 2018



Transcript: 

Joyce A. O’Shaughnessy, MD: When we put the single-agent platinum data, like from the Isakoff trial, and compare it with the PARP inhibitor data, response rates are very, very similar; very high in the 60% range. PFS is about the same but it’s much less toxic to get a PARP inhibitor. So, it seems very reasonable, if you know you’ve got a germline BRCA patient, to utilize it early on. We certainly are pretty desperate for data, but what about those other germline mutations, do they benefit or not?

Claudine Isaacs, MD: There are a number of trials ongoing. We have a trial at our institution that is looking at that beyond breast cancer but also beyond BRCA1 and BRCA2, so looking at the variety of the different mutations that fall within that pathway. And there are a number of clinical trials that are addressing that question. So, I think we’ll get some answers pretty soon.

Joyce A. O’Shaughnessy, MD: Yes, and we have trials we can put our patients on in the meantime if we have that.

Claudine Isaacs, MD: Joyce, just one last thing to talk about in the BRCA space. We do have the metastatic trial that was presented a couple of years ago focusing specifically on BRCA1 and BRCA2 carriers, randomizing to platinum versus a taxane, showing that the outcome was much better in terms of response rate and duration of response with a platinum. So, we’re thinking of sequencing, but 1 of the 2 things that I would have on my roster for those patients would be a platinum. And, again, this is not in patients who progressed very recently having been on a platinum in the neoadjuvant or adjuvant setting and PARP inhibitors.

Joyce A. O’Shaughnessy, MD: Right, the TNT trial.

Claudine Isaacs, MD: The TNT trial.

Joyce A. O’Shaughnessy, MD: It has a level 1 evidence that BRCA patients really benefitted way more from a platinum than from taxane. Olaparib and talazoparib, pretty similar level of efficacy, data pretty close, and a little bit more heme toxicity with the talazoparib, particularly anemia as I recall, which probably is going to be manageable with some dose reductions for a certain number of patients. Any other distinguishing points that you would say about the agents?

Tiffany Traina, MD: I guess just one other trial piece is that the EMBRACA trial with talazoparib did allow for women who had prior history of brain metastases. So, I think about 15% of patients on that trial had prior brain metastases.

Joyce A. O’Shaughnessy, MD: That’s right, and the Forest plot showed that they got the same, quite large, benefit. The hazard ratio was in the 0.3 range in favor of the talazoparib, which means maybe that if you have a patient with brain metastases, once talazoparib is available, take it. Of course, we’re going to need some more data looking specifically at that question, but that’s a very important subset that really came out there. If we had a choice between the 2, we have a patient with brain metastases, which unfortunately is not uncommon, we might consider the old talazoparib for that patient. Real nice point.

Transcript Edited for Clarity 

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Transcript: 

Joyce A. O’Shaughnessy, MD: When we put the single-agent platinum data, like from the Isakoff trial, and compare it with the PARP inhibitor data, response rates are very, very similar; very high in the 60% range. PFS is about the same but it’s much less toxic to get a PARP inhibitor. So, it seems very reasonable, if you know you’ve got a germline BRCA patient, to utilize it early on. We certainly are pretty desperate for data, but what about those other germline mutations, do they benefit or not?

Claudine Isaacs, MD: There are a number of trials ongoing. We have a trial at our institution that is looking at that beyond breast cancer but also beyond BRCA1 and BRCA2, so looking at the variety of the different mutations that fall within that pathway. And there are a number of clinical trials that are addressing that question. So, I think we’ll get some answers pretty soon.

Joyce A. O’Shaughnessy, MD: Yes, and we have trials we can put our patients on in the meantime if we have that.

Claudine Isaacs, MD: Joyce, just one last thing to talk about in the BRCA space. We do have the metastatic trial that was presented a couple of years ago focusing specifically on BRCA1 and BRCA2 carriers, randomizing to platinum versus a taxane, showing that the outcome was much better in terms of response rate and duration of response with a platinum. So, we’re thinking of sequencing, but 1 of the 2 things that I would have on my roster for those patients would be a platinum. And, again, this is not in patients who progressed very recently having been on a platinum in the neoadjuvant or adjuvant setting and PARP inhibitors.

Joyce A. O’Shaughnessy, MD: Right, the TNT trial.

Claudine Isaacs, MD: The TNT trial.

Joyce A. O’Shaughnessy, MD: It has a level 1 evidence that BRCA patients really benefitted way more from a platinum than from taxane. Olaparib and talazoparib, pretty similar level of efficacy, data pretty close, and a little bit more heme toxicity with the talazoparib, particularly anemia as I recall, which probably is going to be manageable with some dose reductions for a certain number of patients. Any other distinguishing points that you would say about the agents?

Tiffany Traina, MD: I guess just one other trial piece is that the EMBRACA trial with talazoparib did allow for women who had prior history of brain metastases. So, I think about 15% of patients on that trial had prior brain metastases.

Joyce A. O’Shaughnessy, MD: That’s right, and the Forest plot showed that they got the same, quite large, benefit. The hazard ratio was in the 0.3 range in favor of the talazoparib, which means maybe that if you have a patient with brain metastases, once talazoparib is available, take it. Of course, we’re going to need some more data looking specifically at that question, but that’s a very important subset that really came out there. If we had a choice between the 2, we have a patient with brain metastases, which unfortunately is not uncommon, we might consider the old talazoparib for that patient. Real nice point.

Transcript Edited for Clarity 
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