The Path Forward in Breast Cancer Research



Adam M. Brufsky, MD, PhD: I think we’ve gone through a lot of different things today, but we really hit a lot of the highlights, especially what’s being presented at ESMO. And so, this has been a really informative discussion. Before we end, I’d like to get final thoughts from all of the panelists, and I’ll start with Dr. Gnant. Do you have any final thoughts?

Michael Gnant, MD: We live in a fascinating era, we have so much great news for our patients, and we see innovation in a constant pattern with the ability to prolong our patients’ lives, to eventually increase cure rates, and to provide a better quality of life. So, this is fascinating. I do believe that the best breakthrough is probably the large standard-of-care—changing trials being done in academic collaboration with industry and with networks. We are going to focus on biomarkers and response prediction because we have to. Otherwise, even the most affluent countries will not be able to afford all these innovations for all of our patients in the next decade.

Adam M. Brufsky, MD, PhD: Very good. Joyce?

Joyce A. O’Shaughnessy, MD: It is reflecting that we’re getting more and more tools to improve overall outcomes in the curative setting. We’re continuing to make progress. In triple-negative breast cancer, we are hearing about survival in the GeparSixto trial, albeit in a regimen that’s not used standardly around the globe. But nonetheless, there’s an addition of carboplatin with overall survival. We saw a hint in the BrighTNess trial of a big improvement in pathologic CR rate with the addition of carboplatin to weekly paclitaxel followed by AC [doxorubicin (Adriamycin) and cyclophosphamide], a very large improvement. And in all of the data, very early and preliminary, there was improvement in disease-free survival that appears to potentially be developing with the carboplatin.

We’ll hold that thought. We need more data, certainly on carboplatin, but it’s encouraging. We’ve seen from the CREATE-X data improvements in disease-free and overall survival in those patients who do not have a pathologic CR with triple-negative breast cancer, so there’s some benefit there. There are other agents coming along that look promising. Certainly, we have high hopes for the checkpoint inhibitors and the PARP inhibitors, hopefully in the OLYMPIAD trial, in the adjuvant setting. And of course, HER2-positive disease has seen dramatic improvement, and now we have neratinib to bring in there to get an additional 4% at 5 years for patients. And then we’re coming in with the CDK4/6 inhibitors, which will very likely benefit patients with aggressive biology who are still at risk for recurrence. And then, I have high hopes that we will find the right population, those with a PIK3CA mutation. So, I think we’re just continuing to make really important progress in patients and keep moving toward preventing recurrence.

Adam M. Brufsky, MD, PhD: Hope?

Hope S. Rugo, MD: It’s hard to add to all of that, but I certainly agree. I think what we’ve learned from the new therapies is that we can give targeted agents that do not have as much toxicity as those agents we put up with earlier, targeted agents that didn’t work as well. So, that’s very exciting. I think we do need to identify the patients who are most likely to benefit. I think the name of the game for all of us is to move these drugs into early stage setting as quickly as possible, the agents we think are highly effective, so that we can cure more women with breast cancer.

One of the most exciting things to me is to use the neoadjuvant setting—we talk a lot about it as a laboratory—as a way to decide who needs more versus who needs less, both in endocrine therapy with targeted agents and in chemotherapy with targeted agents, and to decide the type of chemotherapy we use. We’re really moving in that direction now, which I think is very exciting.

There are some alternatives to chemotherapy that are out there as well with some exciting data: these antibody drug conjugates. That’s a whole other area that’s being explored, where we have only the HER2-targeted agent, trastuzumab emtansine. But there are a number of agents potentially coming down the pipe for triple negative disease. So, I think that’s also really exciting.

And then lastly, to really echo what Michael said about the fact that we, not to sound tripe, are a village. We’re not going to get any of this work done unless we can collaborate across countries, between academics and the pharmaceutical industry, to make the best possible trials that serve our patients in the best way.

Adam M. Brufsky, MD, PhD: Agreed. And finally, Michael. Any comments?

Michael Untch, MD: I finish by quoting the St. Gallen’s motto of this year, which was, “de-escalation, escalation.” In patients who have aggressive disease, we know that escalation might be a way to go: double blockade; the addition of neratinib in patients with HER2-positive disease; the addition of platinum in patients with triple-negative breast cancer. CDK4/6 inhibitors are on their best way to being included in adjuvant trials, such as the PALLAS trial. The early trials with ribociclib and abemaciclib will go into adjuvant trials. That means another chemotherapy escalation, because this is the type of aggressive disease, luminal cancer, that definitely doesn’t always need chemotherapy. We might go for an escalation with a targeted agent, which is CDK4/6 inhibition. And last but not least, de-escalation. This is a dream for all of us, to use less aggressive therapy than chemotherapy. We Germans are not quite known to be de-escalators, but we are learning from the rest of the world. I’m happy to share my thoughts with my dear colleagues here and be part of this event. Thank you so much.

Adam M. Brufsky, MD, PhD: Great. Thank you very much. Thanks to all of you for your contributions to this discussion. And on behalf of the panel, we thank you for joining us and hope you found this Peer Exchange® discussion to be useful and informative.

Transcript Edited for Clarity

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