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Role of Neoadjuvant Platinum-Based Therapy for TNBC

Panelists: Adam M. Brufsky, MD, PhD, University of Pittsburgh Cancer Institute; Michael Gnant, MD, Medical University of Vienna; Joyce A. OShaughnessy, MD, Baylor University Medical Center; Hope S. Rugo, MD, University of California San Francisco Helen Diller Family Comprehensive Cancer Center; Michael Untch, MD, Helios Klinikum Berlin-Buch
Published Online: Monday, Nov 13, 2017



Transcript: 

Adam M. Brufsky, MD, PhD: Where does carboplatin fit it? You’re presenting data on carboplatin, at least in the neoadjuvant setting, with these patients. Where does carboplatin fit into this?

Michael Untch, MD: We presented data on survival from the GeparSixto trial at this meeting. It was a neoadjuvant trial powered for pCR, but obviously we now have 5-year disease-free over survival data. We have a survival benefit in GeparSixto with the addition of platinum chemotherapy, but unfortunately, I have to confess that in the control arm, we didn’t take the alkylating agent, cyclophosphamide. Now we have done a similar trial in which Hope Rugo and myself were involved. The BrighTNess trial was presented at ASCO 2017. It was a positive trial for the addition of platinum, and it was not positive for the addition of veliparib, another PARP inhibitor, to platinum. So basically, the pCR as an endpoint could not be made better with the addition of veliparib in patients who had already a significant benefit for platinum.

In Germany now, as a national guideline for patients with triple-negative breast cancer, we use platinum on a routine basis in the neoadjuvant setting in addition to anthracycline and taxanes. I’m excited about all of the PARP inhibitors. I would not say which of the PARP inhibitors that are coming now or are already on the market is better or not, and it seems that I’m the only GI oncologist here at this table. I treat a lot of ovarian cancer patients. Now in ovarian cancer, PARP inhibition is one of the successful stories of the last few years. We have olaparib approved, and we have now neratinib approved from Tesaro. These 2 drugs make the natural history of this devastating disease very different. I have long-time responders of more than 2 years, with the addition of a PARP inhibitor in patients who otherwise would have died of their ovarian cancer.

Adam M. Brufsky, MD, PhD: That’s interesting. In ovarian cancer, though, you use it as consolidation, right?

Michael Untch, MD: As consolidation.

Adam M. Brufsky, MD, PhD: You use platinum-based therapy and then consolidation. Is that a strategy in breast cancer?

Michael Untch, MD: Joyce gave a very good example. It was an anecdotal example, but I liked this example because it fits in with the ovarian cancer story.

Michael Gnant, MD: This is what’s going to hopefully be, or actually is, on the way in the early breast cancer setting. In the adjuvant OLYMPIAD trial, this is what we did. I think it is clearly fascinating that we have been discussing a lot with luminal subtypes, catching up with HER2-positive disease. And finally, for triple-negative disease—we were more or less desperate for a decade or so—there is now innovation that’s going to benefit our patients. What I’m interested in is that it appears to be very clear for germline-mutated patients, but obviously there are other patients.

Adam M. Brufsky, MD, PhD: Who should benefit?

Michael Gnant, MD: We should recognize what test to use.

Adam M. Brufsky, MD, PhD: Who has BRCA mutations? Who is PARP-i7 high? What should we be using?

Hope S. Rugo, MD: Well that’s a problem.

Michael Gnant, MD: The potential of this is that it can probably expand, approximately double, the number of patients who can benefit from these innovative agents.

Adam M. Brufsky, MD, PhD: I have 1 question. I know it’s uncommon, but I’ve started to see a few somatic BRCA mutations. If you did a foundation or some next-generation sequencing and found a somatic mutation, would these drugs work? Would these agents work?

Michael Untch, MD: We have the experience from ovarian cancer, and it has been proven that patients who do not have a germline mutation, but have a somatic mutation, have an excellent response to this class of drugs.

Adam M. Brufsky, MD, PhD: So, we do have evidence from other diseases.

Michael Untch, MD: We have evidence.

Hope S. Rugo, MD: The niraparib trial showed that, but it’s such a different disease.

Michael Untch, MD: Again, it’s ovarian cancer, but let’s do some more clinical work, some more trials. I expect to see a very similar story in triple-negative breast cancer.

Transcript Edited for Clarity 

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Transcript: 

Adam M. Brufsky, MD, PhD: Where does carboplatin fit it? You’re presenting data on carboplatin, at least in the neoadjuvant setting, with these patients. Where does carboplatin fit into this?

Michael Untch, MD: We presented data on survival from the GeparSixto trial at this meeting. It was a neoadjuvant trial powered for pCR, but obviously we now have 5-year disease-free over survival data. We have a survival benefit in GeparSixto with the addition of platinum chemotherapy, but unfortunately, I have to confess that in the control arm, we didn’t take the alkylating agent, cyclophosphamide. Now we have done a similar trial in which Hope Rugo and myself were involved. The BrighTNess trial was presented at ASCO 2017. It was a positive trial for the addition of platinum, and it was not positive for the addition of veliparib, another PARP inhibitor, to platinum. So basically, the pCR as an endpoint could not be made better with the addition of veliparib in patients who had already a significant benefit for platinum.

In Germany now, as a national guideline for patients with triple-negative breast cancer, we use platinum on a routine basis in the neoadjuvant setting in addition to anthracycline and taxanes. I’m excited about all of the PARP inhibitors. I would not say which of the PARP inhibitors that are coming now or are already on the market is better or not, and it seems that I’m the only GI oncologist here at this table. I treat a lot of ovarian cancer patients. Now in ovarian cancer, PARP inhibition is one of the successful stories of the last few years. We have olaparib approved, and we have now neratinib approved from Tesaro. These 2 drugs make the natural history of this devastating disease very different. I have long-time responders of more than 2 years, with the addition of a PARP inhibitor in patients who otherwise would have died of their ovarian cancer.

Adam M. Brufsky, MD, PhD: That’s interesting. In ovarian cancer, though, you use it as consolidation, right?

Michael Untch, MD: As consolidation.

Adam M. Brufsky, MD, PhD: You use platinum-based therapy and then consolidation. Is that a strategy in breast cancer?

Michael Untch, MD: Joyce gave a very good example. It was an anecdotal example, but I liked this example because it fits in with the ovarian cancer story.

Michael Gnant, MD: This is what’s going to hopefully be, or actually is, on the way in the early breast cancer setting. In the adjuvant OLYMPIAD trial, this is what we did. I think it is clearly fascinating that we have been discussing a lot with luminal subtypes, catching up with HER2-positive disease. And finally, for triple-negative disease—we were more or less desperate for a decade or so—there is now innovation that’s going to benefit our patients. What I’m interested in is that it appears to be very clear for germline-mutated patients, but obviously there are other patients.

Adam M. Brufsky, MD, PhD: Who should benefit?

Michael Gnant, MD: We should recognize what test to use.

Adam M. Brufsky, MD, PhD: Who has BRCA mutations? Who is PARP-i7 high? What should we be using?

Hope S. Rugo, MD: Well that’s a problem.

Michael Gnant, MD: The potential of this is that it can probably expand, approximately double, the number of patients who can benefit from these innovative agents.

Adam M. Brufsky, MD, PhD: I have 1 question. I know it’s uncommon, but I’ve started to see a few somatic BRCA mutations. If you did a foundation or some next-generation sequencing and found a somatic mutation, would these drugs work? Would these agents work?

Michael Untch, MD: We have the experience from ovarian cancer, and it has been proven that patients who do not have a germline mutation, but have a somatic mutation, have an excellent response to this class of drugs.

Adam M. Brufsky, MD, PhD: So, we do have evidence from other diseases.

Michael Untch, MD: We have evidence.

Hope S. Rugo, MD: The niraparib trial showed that, but it’s such a different disease.

Michael Untch, MD: Again, it’s ovarian cancer, but let’s do some more clinical work, some more trials. I expect to see a very similar story in triple-negative breast cancer.

Transcript Edited for Clarity 
View Conference Coverage
Online CME Activities
TitleExpiration DateCME Credits
Medical Crossfire®: Leveraging New Evidence in the Context of Evolving Early-Stage Treatment Standards in HER2-Positive Breast CancerJan 30, 20181.5
14th Annual School of Breast Oncology® OnlineFeb 10, 201825
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