Dr. Jennifer Litton, a board-certified medical oncologist and professor of breast medical oncology at the University of Texas MD Anderson Cancer Center in Houston, where she is chief of the Section of Clinical Research and Drug Development for Breast Cancer. She also is a member of the Breast Immuno-Oncology Task Force of the National Cancer Institute.
At the American Association for Cancer Research virtual annual meeting, Dr. Litton presented results from the EMBRACA trial, looking at using Talzenna (chemical name: talazoparib), a type of medicine called a PARP inhibited, to treat advanced-stage HER2-negative breast cancer in people with a BRCA1 or BRCA2 mutation. She joins us today to talk about the results, especially the patient-reported outcomes, which showed that people treated with Talzenna had better quality of life than people treated with chemotherapy.
Listen to the podcast to hear Dr. Litton explain:
- what a PARP inhibitor is and how it works
- how quality of life was better for people treated with Talzenna compared to chemotherapy
- why she thinks Talzenna is a good treatment option for people diagnosed with metastatic HER2-negative breast cancer who also have a BRCA1 or a BRCA2 mutation
Running time: 14:04
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Show Full Transcript
Jamie DePolo: Hello, thanks for listening. Our guest is Dr. Jennifer Litton, a board-certified medical oncologist and professor of breast medical oncology at the University of Texas MD Anderson Cancer Center in Houston, where she is chief of the Section of Clinical Research and Drug Development for Breast Cancer. She also is a member of the Breast Immuno-Oncology Task Force of the National Cancer Institute.
At the American Association for Cancer Research Virtual Annual Meeting, Dr. Litton presented results from the EMBRACA trial, looking at using Talzenna, a type of medicine called a PARP inhibitor, to treat advanced HER2-negative breast cancer in people with a BRCA1 or BRCA2 mutation. She joins us today to talk about the results, especially the patient-reported outcomes, which showed that people treated with Talzenna had better quality of life than people treated with chemotherapy.
Dr. Litton, welcome to the podcast. It’s so nice to talk to you again.
Jennifer Litton: Oh, thank you very much, Jamie, and to Breastcancer.org for inviting me to talk about the EMBRACA trial.
Jamie DePolo: Yes. We’re very excited to hear about it. Now, just so everybody knows, could you explain what a PARP inhibitor is and how it works?
Jennifer Litton: Sure. So, a PARP inhibitor… We get mistakes in our DNA all the time during cell division or other exposures, and we have many different ways that our cells and our bodies fix these mistakes so that the cells can divide or get fixed or get killed off. Now, PARP is one of the important enzymes in one of the ways that we can repair DNA, just like BRCA is a gene that encodes for a protein that’s important in a whole other way that we repair DNA.
So, when someone has, say, a BRCA mutation, the cancer cells can start to rely heavily on the PARP pathway to repair their DNA. And so blocking that pathway, the cancer cells, they can’t divide, and they die off.
Now, for these PARP inhibitors, not only just blocking the enzyme, but we’re also finding that it’s something called PARP trapping, where once there’s a nick in that DNA, the PARP inhibitor goes onto the DNA, and then it won’t release, and it’s another way of really blocking that repair and trying to help that cancer cell die off.
Jamie DePolo: So, it almost has like, two mechanisms of action, it sounds like.
Jennifer Litton: Yes. We’re learning all the time, but there are two ways of blocking that same enzyme and blocking that DNA repair.
Jamie DePolo: Okay. Thank you. So, I know we’ve talked about the EMBRACA trial in the past at one of those San Antonio Breast Cancer Symposiums, but if you could briefly describe the study and what the goals were?
Jennifer Litton: Sure. So, the EMBRACA trial was an international, multicenter trial that includes 431 patients who were randomized two-to-one to either receive talazoparib, which is an oral PARP inhibitor — it’s given once daily — versus physician’s choice of chemotherapy, and there were four different chemotherapy options.
The primary goal of the trial was to look at progression-free survival, and at that first look when we reached the criteria to look for progression-free survival, there was an improvement with a hazard ratio of 0.54, and it was statistically significant. Based on that, PARP inhibitor talazoparib went on to get different approval to treat patients with metastatic breast cancer who had a germline BRCA mutation.
Jamie DePolo: And as you said, these earlier results that you presented showed that Talzenna, or talazoparib, improved progression-free survival, But your latest results, presented at AACR, showed that overall survival was about the same, whether people got Talzenna or whether they were treated with chemotherapy. So, could you talk a little bit about that? I know there is sometimes a little bit of controversy over progression-free survival versus overall survival.
Jennifer Litton: Sure. Absolutely. So, that’s exactly right. One of the things about the EMBRACA trial, it was a fairly large study. In fact, it was the largest study looking at BRCA mutation carriers in a randomized fashion. The overall survival was triggered by a number of events, and it did not meet the statistical significance. You know, I certainly wished it did, but I don’t think that that decreases from the overall efficacy of this drug or other drugs that meet a progression-free survival endpoint. As we’re treating patients with breast cancer and metastatic breast cancer, we have more and more therapies. Women are definitely living longer than they did when I first started treating breast cancer patients, and there are so many different confounding effects of different therapies that we use as to what adds to overall survival or not.
So, absolutely, it’s always better to show overall survival, but I do think that that doesn’t take away, necessarily, from PARP inhibitors being a good option for patients with metastatic breast cancer and a germline BRCA. That’s for several reasons. One, the response rate of EMBRACA, which goes along with what we saw in the OlympiAD trial with the PARP inhibitor olaparib — so I would really see this as a class effect — had a very high response rate, over 60% from both of those trials, which was much higher than we saw in response to the chemotherapy. So, what that means is that tumors were actually shrinking at a much higher rate.
And what’s also really telling — and again, in both trials and what we presented in EMBRACA for AACR — was that when we looked at patient-reported outcomes… So, patients were asked about their quality of life throughout the study in both arms. What was really important to me and for my patients is that the patients who were randomized to talazoparib, actually, their quality of life overall improved versus those who were randomized to chemotherapy, and they overall had a decrease in their quality of life. And when we looked at the time to meaningful clinical deterioration for patients with metastatic cancer, it was significantly improved in patients who were randomized to talazoparib versus those who were randomized to the physician’s choice of chemotherapy. So, it’s not just the progression-free survival. It’s also that patients overall felt better on one therapy than the other, and that’s really important for breast cancer patients.
And the other interesting thing, which was absolutely not planned, but we went to look at it just to see, was there a difference, is that during the time of EMBRACA, other PARP inhibitors became commercially available. And subsequently, over 30% of patients who were randomized to chemotherapy went on to receive a subsequent PARP inhibitor, and over 40% in both arms went on to receive platinum compound, also shown to be very efficacious in patients with metastatic breast cancer and a known germline BRCA mutation.
So, there were a lot of interesting confounding effects, potentially, on the backend of the treatments after people progressed on the EMBRACA trial. So, very interesting to show that people continued to go on to get multiple other lines of therapy.
Jamie DePolo: Yeah. I do want to ask you about the quality of life because that’s what really stood out for me. That seems really important. Could you explain just a little bit? Like, when you say quality of life, what did that mean? What were these people reporting?
Jennifer Litton: Sure. So, we actually used very well-defined tools for patients to measure their quality of life. These are validated surveys that they took at different timepoints. And when they looked at the EORTC QLQ-C30 measurement, which kind of looks at global quality of life, in addition to even when we looked at breast cancer-specific, we had improvements in their scores and how they were rating how they were doing, versus decreasing in patients who were randomized to the chemotherapy.
Jamie DePolo: Okay. So, I’m assuming that includes things like side effects or fatigue, pain… is that accurate?
Jennifer Litton: It is. And we used several different tools to look at that, side effects, all of that. The only thing that was different is that patients on talazoparib did have a higher rate, about 24%, of some grade 1 hair loss. That was one of the things that when we kind of tried to drill down on the side effects, people were hoping with that pill not to have any hair loss at all. But 25% had some grade 1. I think only one or two had full grade 2, like the patients with the chemotherapy.
Jamie DePolo: Okay. Okay. Well, that’s very good to know. And I know quality of life is really, really important to a lot of people who are being treated for breast cancer, and I guess, cancer just in general. To your mind, do you think that difference in quality of life, does that make Talzenna a better option than chemotherapy for advanced-stage HER2-negative breast cancer, if somebody has a BRCA1 or BRCA2 mutation?
Jennifer Litton: Sure. I think, absolutely, in the sense that, for so many reasons, we had a much higher percentage of people actually have their tumors shrink. They felt better.
Don’t forget, just taking a pill instead of going in, waiting for the blood and the infusion room, being hooked up to the chemotherapy — which is what my patients tell me all the time, the idea of just, “I can take it at 1:00, at my home, right after lunch.” It’s freeing for a lot of people when they know, with metastatic cancer and they’re always going to be on a therapy, that anything that takes them away from their family and other things that they want to be doing in a day, I think is a really big deal. And if we can provide a therapy that makes you feel better, has a higher response rate, and you take once a day? I think that’s really significant.
Jamie DePolo: Yes. That’s very important. Thank you. So, to sort of wrap up, could you summarize what you’d like people to take way from these latest results from the EMBRACA trial?
Jennifer Litton: Sure. I think that for patients with metastatic breast cancer and a germline BRCA mutation, PARP inhibitors — and in this case, we’re talking about the EMBRACA trial and talazoparib — I do think is a very good option for patients for a therapy choice due to the ease of administration, the improvement of quality of life, improvement in progression-free survival, as well.
I certainly always wish we could see overall survival, but again, as we discussed, there’s so much that different treatments, different lines of therapy that goes into patients with metastatic cancer, we’re learning all the time and more therapies. I would definitely offer this to my patients based on this.
I’m also very intrigued by the ongoing research of how to make PARP inhibitors and have the effects last longer, how to use them in different combinations to have more patients be able to benefit, outside of patients with the known germline BRCA1 and [BRCA]2 mutation. And I’ll stay tuned because the DNA damage repair pathways are complex with a lot of very intriguing targets and new drugs that are being actively developed, and we will hear a lot more from PARP inhibitors and other inhibitors of the DNA damage repair pathway.
Jamie DePolo: Dr. Litton, thank you so much.
Jennifer Litton: Thank you.
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