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NCCN Guideline Changes for BRCA Testing in TNBC

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: Am I right, did the NCCN recently come out and say that they supported the approach of testing all of our HER2-negative metastatic patients for BRCA1 and BRCA2? I believe that has been recently added to the NCCN guidelines. I had heard that and I was surprised to hear it, so I went and looked myself on the NCCN. So, that’s actually pretty good. We don’t have to only do it per the NCCN guidelines for the early stage, but in the metastatic and the HER2-negative, it makes sense with a novel therapeutic available now for patients that it is actually supported by NCCN for anybody to just check that BRCA1 and BRCA2. So, what do you think? Is that going to be something that makes sense in your practice and would you use these first-line therapies pretty much in everybody or selectively in the germline BRCA1 and BRCA2s?

Aditya Bardia, MD, MPH: I would concur with what Claudine had mentioned that in this day and age, anyone with metastatic triple-negative breast cancer, we should be considered BRCA testing. We know that triple-negative breast cancer has an aggressive tumor biology, and here you have a drug that is oral and has activity. Even if I miss 2 patients who otherwise would not have been or I identified 2 patients who otherwise would not have been the classic family history with BRCA carriers, I would be happy. So, I think it’s very reasonable to test anyone with metastatic triple-negative breast cancer for BRCA testing. Now, in terms of new therapies, we have olaparib and we have talazoparib, and I think the results were very similar. There are some differences between these agents in terms of their potency, so talazoparib is more potent than olaparib. It also has the PARP trapping. Whether that would have clinical significance, we don’t know. It’s tough to compare 2 different trials, but the hazard ratios were pretty similar. If you look at the side effect profile, the talazoparib had slightly more heme toxicity and that could be because it’s more potent, but also, we need to be cautious when we are comparing 2 different trials.

Now, in terms of where I would use it, if I have a patient with bona fide germline BRCA mutation, I would feel comfortable using it as a first-line or definitely as a second-line agent, particularly for triple-negative breast cancer. It’s a difficult discussion in ER-positive metastatic breast cancer, should I use a CDK4/6 inhibitor versus a PARP inhibitor as first-line therapy? But given the data we have with CDK4/6 inhibitors and because there should not be any cross resistance between a CDK4/6 and PARP, in ER-positive setting, I would probably use a CDK4/6 as first-line therapy and consider PARP as second-line or third-line therapies.

Tiffany Traina, MD: Not surprisingly, there are trials that are in design looking at that combination for ER-positive, a CDK4/6 inhibitor plus PARP inhibition, trying to move that up a little bit.

Joyce A. O’Shaughnessy, MD: Wow, that’s interesting.

Claudine Isaacs, MD: And I think the point to make, in the clinical trial as well they did that. The comment was the patients who had ER-positive/HER2-negative, which comprised about 15% of the population in those trials. So, again, just a reminder to us that BRCA1 and BRCA2 are not just restricted to triple-negative disease. They should have had prior endocrine therapy, so I think it fits very much with what you were thinking and discussing about doing in practice.

Joyce A. O’Shaughnessy, MD: I personally probably definitely with the CDK4/6, personally I’d probably run the gamut of the endocrine therapies as we’ve historically done and then go on to olaparib as a chemotherapy-sparing option probably for the ER-positives.

Transcript Edited for Clarity 

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Transcript: 

Joyce A. O’Shaughnessy, MD: Am I right, did the NCCN recently come out and say that they supported the approach of testing all of our HER2-negative metastatic patients for BRCA1 and BRCA2? I believe that has been recently added to the NCCN guidelines. I had heard that and I was surprised to hear it, so I went and looked myself on the NCCN. So, that’s actually pretty good. We don’t have to only do it per the NCCN guidelines for the early stage, but in the metastatic and the HER2-negative, it makes sense with a novel therapeutic available now for patients that it is actually supported by NCCN for anybody to just check that BRCA1 and BRCA2. So, what do you think? Is that going to be something that makes sense in your practice and would you use these first-line therapies pretty much in everybody or selectively in the germline BRCA1 and BRCA2s?

Aditya Bardia, MD, MPH: I would concur with what Claudine had mentioned that in this day and age, anyone with metastatic triple-negative breast cancer, we should be considered BRCA testing. We know that triple-negative breast cancer has an aggressive tumor biology, and here you have a drug that is oral and has activity. Even if I miss 2 patients who otherwise would not have been or I identified 2 patients who otherwise would not have been the classic family history with BRCA carriers, I would be happy. So, I think it’s very reasonable to test anyone with metastatic triple-negative breast cancer for BRCA testing. Now, in terms of new therapies, we have olaparib and we have talazoparib, and I think the results were very similar. There are some differences between these agents in terms of their potency, so talazoparib is more potent than olaparib. It also has the PARP trapping. Whether that would have clinical significance, we don’t know. It’s tough to compare 2 different trials, but the hazard ratios were pretty similar. If you look at the side effect profile, the talazoparib had slightly more heme toxicity and that could be because it’s more potent, but also, we need to be cautious when we are comparing 2 different trials.

Now, in terms of where I would use it, if I have a patient with bona fide germline BRCA mutation, I would feel comfortable using it as a first-line or definitely as a second-line agent, particularly for triple-negative breast cancer. It’s a difficult discussion in ER-positive metastatic breast cancer, should I use a CDK4/6 inhibitor versus a PARP inhibitor as first-line therapy? But given the data we have with CDK4/6 inhibitors and because there should not be any cross resistance between a CDK4/6 and PARP, in ER-positive setting, I would probably use a CDK4/6 as first-line therapy and consider PARP as second-line or third-line therapies.

Tiffany Traina, MD: Not surprisingly, there are trials that are in design looking at that combination for ER-positive, a CDK4/6 inhibitor plus PARP inhibition, trying to move that up a little bit.

Joyce A. O’Shaughnessy, MD: Wow, that’s interesting.

Claudine Isaacs, MD: And I think the point to make, in the clinical trial as well they did that. The comment was the patients who had ER-positive/HER2-negative, which comprised about 15% of the population in those trials. So, again, just a reminder to us that BRCA1 and BRCA2 are not just restricted to triple-negative disease. They should have had prior endocrine therapy, so I think it fits very much with what you were thinking and discussing about doing in practice.

Joyce A. O’Shaughnessy, MD: I personally probably definitely with the CDK4/6, personally I’d probably run the gamut of the endocrine therapies as we’ve historically done and then go on to olaparib as a chemotherapy-sparing option probably for the ER-positives.

Transcript Edited for Clarity 
View Conference Coverage
Online CME Activities
TitleExpiration DateCME Credits
Cancer Summaries and Commentaries™: Update from Chicago: Advances in the Treatment of Breast CancerJul 31, 20181.0
Community Practice Connections™: Medical Crossfire®: Translating Lessons Learned with PARP Inhibition to the Treatment of Breast Cancer—Expert Exchanges on Novel Strategies to Personalize CareAug 29, 20181.5
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