[00:00:00] Adam Walker: From Susan G Komen, this is Real Pink, a podcast exploring real stories, struggles, and triumphs related to breast cancer. We’re taking the conversation from the doctor’s office to your living room.
Today is triple negative breast cancer day, an annual opportunity to bring more awareness to this aggressive type of breast cancer that is difficult to treat because it lacks estrogen, progesterone, and HER2 receptor. It primarily affects younger women and black women and can spread quickly and be deadly if left untreated for too long.
Treatment for TNBC used to include the toughest forms of chemotherapy with debilitating side effects. But we’ve come a long way in how we treat patients with triple negative breast cancer so their outcomes are better. Today we’re speaking with Dr. Heather McArthur of UT Southwestern. She’s a former Susan G Komen grantee, professor and Komen Distinguished Chair in Clinical Breast Cancer Research. Dr. McArthur has been working on a Phase 3 clinical trial called Keynote 522, which is testing whether a specific immunotherapy drug improves overall survival for people with high risk early triple negative breast cancer. Dr. McArthur also, along with her colleagues, are trying to determine If all people with this type of breast cancer truly need the drug and if not who would most benefit from taking it? Dr. McArthur welcome to the show.
[00:01:31] Dr Heather McArthur: Thank you for having me. It’s a pleasure to be here.
[00:01:34] Adam Walker: I really appreciate you joining us this is a really important topic and who better to talk to about it than you so to start could you introduce yourself to our listeners more than I’ve introduced you, of course? And tell us about your interest in triple negative breast cancer and how you came to study and get involved in this particular clinical trial.
[00:01:51] Dr Heather McArthur: Certainly. So my name is Heather McArthur. I’m the clinical director of the breast cancer program at UT Southwestern in Dallas, Texas.
I have a longstanding interest in the application of immune therapy to treat breast cancer in general. So when I worked at Memorial Sloan Kettering Cancer Center in New York many years ago, I had the privilege of working with a fellow named Jim Allison, who got the Nobel Prize a few years ago for his role in identifying one of the key checkpoints that modern immune therapy targets.
So in 2009 we embarked on designing the first, to my knowledge, curative intent immune therapy trial for the treatment of breast cancer and the field has since exploded.
Triple negative breast cancer seems to be the most innately responsive to, immune modulation. But there is emerging data that these are relevant strategies to other subtypes of breast cancer as well.
[00:02:49] Adam Walker: Interesting. Okay. And the results of the trial were recently presented at the San Antonio Breast Cancer Symposium.
So tell us what you and your colleagues are finding and what it means for patient.
[00:03:02] Dr Heather McArthur: In the first report from the Keynote 522 experience, which was several years ago, and again, the Keynote 522 study is a study that enrolled patients with early stage, 2 and 3, triple negative breast cancer, specifically, and randomize them in a large global phase three effort to receive preoperative chemotherapy or neoadjuvant chemotherapy is another commonly applied term with or without the addition of immune therapy in the form of pembrolizumab.
The whole idea of adding immune therapy Is that you can generate an immune response to tumor specific information. So to create a vaccine like effect, that’s the tremendous promise so that if you were faced with that same information at a later date in the form of a tumor recurrence. Ideally, you’re trained immune system would recognize that as bad news and would go into autopilot to eradicate that recurrence.
So that’s the tremendous power. Potentially, harnessing one’s own immune system to recognize and attack one’s own cancer. So in this study, again, randomized women to receive the chemotherapy with or without the immune therapy in the form of Pembrolizumab and in the first reports, we reported on an improvement in pathologic complete response.
In other words, when a patient goes to surgery after their preoperative treatment, the pathologist looks very carefully at the surgical specimen, and if they can’t see any tumor cells left behind, that’s called a pathologic complete response. If there’s one or more cancer cells left behind, that is not a response.
So we first reported on pathologic complete response or the ability to eradicate all the tumor cells, and we showed a 14 percent improvement in pathologic complete response. And the FDA has shown that improvements in pathologic complete response for triple negative breast cancer specifically very highly correlate with curability of disease.
The FDA was not satisfied with this 14 percent improvement in pathologic complete response. They said, we want to see if that actually does indeed improve cure rates in this high risk population and we were later able to show that it did indeed improve event free survival at three years by 7%. So increased cure rates by almost 8 percent as early as three years after diagnosis. So that’s what led to the FDA approval of Pembrolizumab. We have more recently, shown that improval in cure rates translates into an improvement in overall survival.
So an almost 5 percent improvement in overall survival. So longer time on planet earth for a significant proportion of patients, which is terrific. And so that has become a global standard of care now for patients with stage two or three triple negative breast cancer.
[00:05:59] Adam Walker: Wow, that’s amazing. I got chills. That’s so great. That’s a longer time on planet earth. That’s the goal, right? I love that.
[00:06:08] Dr Heather McArthur: It’s very exciting. And as you pointed out, this is a particularly devastating diagnosis, often in a very young population. So these are often your 20-30 year old. And as you pointed out, higher rates of triple negative breast cancer
in certain populations, including African American or black patients, and they can be associated with pregnancy and be neglected, because there’s an assumption that they’re a pregnancy associated presentation. And the reason why this disease is so devastating is not just that it affects young women, but that, I just told you about improvement in three year cure rates, the sort of nuanced message there is that, if the disease comes back at a distant location and becomes metastatic or stage four disease, that typically happens within two to three years of diagnosis.
Historically, the life expectancy for metastatic triple negative breast cancer has been only 12 to 18 months. So you can imagine a 30 year old diagnosed recurs within two to three years and then succumbs to complications of disease. Within a further 12 to 18 months, that’s a less than five year period and is unacceptable for our young patients.
And that’s why we need to move the needle.
[00:07:29] Adam Walker: Yeah, we do. We need them and you’re, doing it. You’re moving the needle. That’s great. I love it. I love it. It’s so important. It’s such important work. I know triple negative breast cancer is one of the more difficult types of breast cancer to treat.
What is the prognosis in treatment look like over the past decades? And what, do you think it’s going to look like for personalized treatment in the future?
[00:07:52] Dr Heather McArthur: So again, we’ve improved cure rates by almost 8 percent with the addition of immune therapy to chemotherapy. It’s worth noting, though, that the chemotherapy backbone that’s required together with immune therapy is comprised of four chemotherapeutic agents.
So it’s a lot of chemotherapy that we have to co administer with immune therapy. And in part because it’s such a difficult disease to treat, we haven’t had a lot of targeted therapies be successful for the treatment of triple negative disease, chemotherapy is not targeted therapy at all, really, which is why you get all the side effects with it.
This 8 percent improvement was really an unprecedented improvement in cure rates for this very high risk population.
[00:08:42] Adam Walker: Yeah.
[00:08:43] Dr Heather McArthur: And again, pathologic complete response is the goal of preoperative treatment because that translates into curability of disease. But even with this new standard of care, 37 percent of patients don’t achieve a pathologic complete response, which was a very high risk of recurrence.
And in fact, about a third of patients with triple negative disease still experience a distant recurrence and develop metastatic disease and some type of that disease I would just make a shout out actually, if you don’t mind, Susan G. Komen, the grant that you mentioned earlier that I was so lucky to receive actually funded research in this very specific space.
So using tumor freezing before surgery and after preoperative treatment to try and invigorate that vaccine like effect that I mentioned earlier. So very grateful to Komen for supporting that research, which is awesome.
[00:09:39] Adam Walker: That’s fantastic. So let’s go back to Keynote 522 for a second. Phase 1 of Keynote 522 started in 2017.
So what have we learned about treating TNBC over the last eight years and which patients would benefit most?
[00:09:55] Dr Heather McArthur: So 8 percent of patients benefit. That means that 92 percent of patients don’t benefit because they’ve even either been cured with the chemotherapy alone. Or their develop metastatic disease, no matter what we do in this modern treatment era.
And unfortunately, we have no biomarkers or any other, correlative studies, whether it be patient characteristics, tumor characteristics that identify up front who that 8% Is that derives benefit and who the 92 percent is who can forego chemotherapy. So that’s the challenge to us right now is to identify biomarkers that allow us to tailor treatment recommendations so that we can give more treatment to those patients who are at higher risk, but deescalate or optimize, minimize treatment for those who don’t need as much treatment. This is a point of note It’s a lot of chemotherapy drugs to co administer with immune therapy.
[00:10:56] Adam Walker: All right. What excites you most about the progress that you’re seeing treating TMBC?
[00:11:04] Dr Heather McArthur: So as I stated earlier, whenever we see benefits in the metastatic setting, we typically move those into the early stage setting to see if we can further improve cure rates and prevent metastatic disease from occurring. The area of antibody drug conjugates, so antibodies that are directed to features of the tumor that are linked to chemotherapeutic drugs offer potentially more targeted or directed treatment to those tumor cells that express the target of interest. There have been, a number of agents that have been successfully explored in the metastatic triple negative breast cancer setting. With clinically important improvements in outcomes in that space, including overall survival.
So time on planet earth with metastatic disease. And so now those agents are being evaluated in the curative intent setting. I’m the global principal investigator for the Tropian Breast 04 clinical trial. That’s a study that’s going head to head against the Keynote 522 regimen that we just described, versus one of these novel antibody drug conjugates together with immune therapy to see if we can further improve on outcomes for patients in terms of curability of disease.
But if we can do that while also minimizing the related toxicity, so a lot of these antibody drug conjugates have much more favorable profiles in that they have just much lower grade toxicity, a lot of them don’t cause the hair loss that our chemotherapeutics cause, and the schedules are a lot more friendly.
So on the terpene breast O4 study, The experimental drug is administered every three weeks, for example, whereas with Keynote 522, you have to come in every week for the first three months. So it’s a lot more patient friendly. So we’re again, hoping that we’re going to, with this strategy, improve cure rates and minimize the toxicity necessary to get there.
And that’s a global phase three study that’s ongoing, three quarters of the way through enrollment. So hoping to see some results from that effort sometime in the coming year.
[00:13:23] Adam Walker: That sounds exciting. So last question, what advice do you have for someone who’s listening to this podcast, who’s facing a triple negative breast cancer diagnosis, or who is a survivor of this subtype?
[00:13:36] Dr Heather McArthur: So my advice to someone with recently diagnosed early stage triple negative breast cancer would be to, request a consultation with a medical oncologist up front. The treatment of triple negative breast cancer really requires multidisciplinary coordination between the surgeon, radiation oncologist, and medical oncologist, and for the vast majority of patients with this diagnosis.
Preoperative drug treatment is indicated. So you want to make sure that you’re having those conversations up front and that drug treatment is considered before planning surgery. And for those people who, have a prior, history of early stage triple negative breast cancer, who have, participated in clinical trials, thank you for your contributions. Because the only way that we can improve outcomes and cure rates for women affected with this disease is through rational, large effort, clinical trial participation, and it takes a lot of bravery. To participate in clinical trials, but it’s the only way that we’re going to further, improve outcomes for future generations.
Thank you to the survivors who have participated in those efforts.
[00:14:50] Adam Walker: That’s right. Thank you very much for that effort. And Dr. McArthur, thank you for what you’re doing. It’s such important work. I really genuinely appreciate the work you’re doing. You’re changing lives and thank you for joining us on the show today.
Thank you so much. As we heard from Dr. McArthur, triple negative breast cancer can be treated and we’ve learned a lot about how we approach treatment with each patient. Keynote 522 is one of the many clinical trials that allow us to personalize care so that every patient gets the treatment that’s right for them and nothing more or nothing less.
Thanks for listening to Real Pink, a weekly podcast by Susan G. Komen. For more episodes, visit realpink.komen.org. And for more on breast cancer, visit komen.org. Make sure to check out @SusanGkomen on social media. I’m your host, Adam. You can find me on Twitter @AJWalker or on my blog, adamjwalker.com.