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Jamie DePolo: Hello, thanks for listening. Dr. Naoto Ueno is professor of breast medical oncology at the University of Texas MD Anderson Cancer Center.
At the European Society for Medical Oncology Congress 2022, Dr. Ueno presented patient-reported outcomes from the DESTINY-Breast04 study, which found that compared to doctor’s choice of chemotherapy, Enhertu improved both progression-free survival and overall survival in people diagnosed with previously treated metastatic, HER2-low breast cancer. Dr. Ueno, welcome to the podcast.
Dr. Naoto Ueno: Great. Thank you very much. I really appreciate having this opportunity to speak with you.
Jamie DePolo: So, just so everyone is kind of on the same page, could you summarize the results from the DESTINY-Breast04 study for us? I believe they were presented at ASCO back in June.
Dr. Naoto Ueno: Right. So, DESTINY-Breast04 study, basically, targets what we call the low HER2-positive disease in a metastatic setting. It was a randomized study between trastuzumab-deruxtecan — we commonly abbreviate this as T-DXd — comparing to physician-choice treatment. The primary endpoint was progression-free survival, meaning that how fast does the disease progress, and then we also looked in at the secondary, overall survival. And we also looked into patient-reported outcome, which is a reflection of what’s the perspective of the patient.
The study basically showed — and it was presented by Dr. Modi in the last ASCO — that T-DXd had a progression-free survival of 8.2 months comparing to physician choice of 3.5 months, which is consistent with chemotherapy, and also it improved the overall survival. So, it was recently approved by FDA in the United States for using T-DXd, commercial name Enhertu, for low HER2-positive metastatic breast cancer.
Jamie DePolo: Thank you. Now, I have to ask you, as an oncologist, these results seemed pretty big. I know Dr. Modi got a 40-second standing ovation when she presented the results at ASCO. So, to you, as somebody treating people with breast cancer, how big are these results? I mean, they sound like they are going to definitely change practice.
Dr. Naoto Ueno: Absolutely. Actually, I didn’t know it was 42 seconds, it felt very long, so I learned something today, 42 seconds!
It’s really exciting, because low HER2-positive, meaning that there [are] two categories: one is people who are hormone-receptor positive, so they are receiving endocrine therapy. The other category, as you know, is triple-negative breast cancer, dominantly treated by chemotherapy.
So, this Enhertu, this T-DXd, is really enriching the chemotherapy to the cancer, and it has a fairly strong response rate and with a very long disease control. So, comparing to the regular chemotherapy, it seems to be really effective, so it really opens up completely new choices for patients who didn’t have an opportunity to receive this treatment, because originally the treatment was indicated for high HER2-positive disease.
So, it is a paradigm shift of bringing in targeted chemotherapy into this type of patient.
Jamie DePolo: Okay. Thanks. Now, in this latest analysis that you presented at ESMO, you were looking at the quality of life of people who were receiving Enhertu compared to people receiving chemotherapy. So, how did you assess quality of life, and could you summarize the results for us, please?
Dr. Naoto Ueno: So, we assessed the patient-reported outcome, which you just talked about quality of life, by using a questionnaire. And there were three different types of questionnaire — and I am not going to go name them — but these are validated questionnaires that’s been used for a long time for other studies, that we know that it does reflect what the patient is feeling.
So, we used these questionnaires during the course of the treatment — for both treatments, Enhertu versus physician’s choice treatment, which is the chemotherapy — and we looked into, basically, how the patient did.
So, what I could tell you from simply summarizing this study is the Enhertu treatment delays the deterioration of quality of life, which means that when the treatment is working very well, patients could maintain a reasonable quality of life, much better comparing to people who are receiving regular chemotherapy.
That’s where the excitement is, because we know that this treatment is effective, we know that it’s safe, and the question is, does the patient feel the same way based on the good efficacy and safety? And we have shown that it does help the patient to maintain a reasonable quality of life by receiving this treatment compared to standard chemotherapy.
Jamie DePolo: Okay, and that sounds very promising and very exciting results. What were the most troubling side effects in each treatment group? Were the side effects similar or does Enhertu cause different side effects than chemotherapy?
Dr. Naoto Ueno: Enhertu has definitely more nausea and vomiting, or basically, what I am trying to say is, anything related [to] gastrointestinal side effects, it’s a little bit more prominent than the others, and also it does cause fatigue.
So, when we looked into the subset of symptoms, fatigue was no different between the two treatments, but when you looked at nausea and vomiting, the first several cycles, there was a clinical significant prominent more nausea and vomiting in the Enhertu side comparing to regular chemotherapy. But it really didn’t further deteriorate, it really stabilized later on, so statistically, there was no difference between the two treatments. But going back to your first question, there is more GI toxicity in this treatment.
Now, this study didn’t reflect this, but the other uniqueness of this treatment is — it’s rare — but it could cause inflammation of the lung, called pneumonitis, and if you let this go, people could die from this pneumonitis. But that’s very small, so it doesn’t reflect in the quality of life very much.
Jamie DePolo: Okay, and that’s something that doctors are aware of and can monitor patients for and let patients know if you do start to have a cough or anything like that, you need to contact your doctor.
Dr. Naoto Ueno: Correct. So, it’s important to let the physician know if you have shortness of breath, fever, and cough. Early detection prevents major deterioration. It’s not common, but it is something that we take very seriously.
Jamie DePolo: Sure. And going back to the nausea and vomiting, if that’s a known side effect of Enhertu, is that something that somebody could take medicine for preventively before the nausea and vomiting even start?
Dr. Naoto Ueno: That is correct. So, Enhertu is considered as moderate nauseating, so they will take a preventive measure, and your physician should know about how to prevent the nausea. Yes.
Jamie DePolo: Okay. Okay. And I just want to confirm, I think I know this, but these side effects that you mentioned, the nausea and vomiting especially, that’s a known side effect of Enhertu. You didn’t see any new side effects in this study?
Dr. Naoto Ueno: No, we did not see anything new. It is a known side effect.
Jamie DePolo: Okay. And then, finally to wrap up, if you could kind of put in context for us, what do you think — the first results from DESTINY-Breast04 and now your results on the quality of life. What do these mean for someone who’s been diagnosed with metastatic breast cancer?
Dr. Naoto Ueno: So, I think if I go in more detail, what does this mean is, I’ve mentioned the quality of life is maintained. And this presentation I did talked about, also, a subset of symptoms related to the survey we did. So, from the pain, physical functioning, emotional functioning, social function, fatigue, everything, it did favor the Enhertu comparing to the regular chemotherapy.
So, you could see that when I talk about the subset data, it gives you a sense that the patient generally did well — much better — comparing to chemotherapy. And because of being HER2 has a much longer prolonged disease control, that prolonged disease control is also reflecting to the daily activity of the patient. You can live with a much better daily life going on with Enhertu comparing to getting chemo, known chemo.
Jamie DePolo: Okay. So, I guess if I could sort of paraphrase you, just to make sure I understand, it sounds like somebody who’s getting Enhertu, they’re better able to kind of get back to life sort of as normal compared to somebody who’s on chemo.
Dr. Naoto Ueno: Right. I wouldn’t say it may be normal, but much more closer to normal comparing to the chemotherapy. Yeah.
Jamie DePolo: Okay.
Dr. Naoto Ueno: And in this case, the choice of the chemo was Xeloda or Halaven or Gemzar or Taxol, you know, the one that everybody knows. And they are also effective, but it’s just that it did favor Enhertu in this study.
Jamie DePolo: Okay. Okay. Well, this sounds very promising. Dr. Ueno, thank you so much for sharing your results with us. I really appreciate it.
Dr. Naoto Ueno: Great. Thank you very much.
