Hi, I’m Jamie DePolo, host of The Breastcancer.org Podcast and senior editor.
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Welcome to The Breastcancer.org Podcast, the podcast that brings you the latest information on breast cancer research, treatments, side effects, and survivorship issues through expert interviews, as well as personal stories from people affected by breast cancer. Here’s your host, Breastcancer.org Senior Editor Jamie DePolo.
Jamie DePolo: Hi, I’m Jamie DePolo, senior editor of Breastcancer.org. I’m podcasting live from the 2025 San Antonio Breast Cancer Symposium. I’m joined by Dr. Aditya Bardia, professor of medicine at the David Geffen School of Medicine at UCLA and director of translational research integration at the UCLA Health Jonsson Comprehensive Cancer Center. At the conference, he presented research on giredestrant, a new oral SERD, a selective estrogen degrader or downregulator for early-stage hormone receptor-positive breast cancer. He's going to explain the research to us. Dr. Bardia, thanks for joining us.
Dr. Aditya Bardia: Thank you so much for having me.
Jamie DePolo: So, there are two other oral SERDs, Orserdu and Inluriyo, also called imlunestrant. So, can you tell us a little bit how giredestrant is different?
Dr. Aditya Bardia: Imlunestrant as well as elacestrant are selective estrogen receptor degraders. Giredestrant is also a selective estrogen receptor degrader. So, these are all what we would call oral SERDs. They bind to the estrogen receptor and degrade it. In terms of how they are different, the side effect profile with these drugs is slightly different. Elacestrant tends to cause more nausea. Imlunestrant tends to cause more diarrhea, while with giredestrant, we tend to see asymptomatic bradycardia.
Jamie DePolo: Okay, and in your presentation, I know that Orserdu and imlunestrant, they're both approved for metastatic or advanced-stage disease. You looked at using giredestrant for early-stage disease, and you also mentioned that it's been shown to work better than both tamoxifen and the aromatase inhibitors. So, can you talk about that? What's unique about giredestrant?
Dr. Aditya Bardia: Yeah. Absolutely. Giredestrant is an oral SERD. In the metastatic setting, we recently saw results from a trial called evERA, which looked at giredestrant plus everolimus, also standard of care endocrine therapy, which would include fulvestrant or AI plus everolimus, and there was improvement in progression-free survival and trend towards improvement in overall survival, as well, but this was in the metastatic setting. In lidERA, we evaluated giredestrant in early breast cancer, where it was compared head-to-head against tamoxifen or aromatase inhibitors, and that's the standard of care at this time. The standard of care for a patient with early-stage ER-positive breast cancer are other AIs or tamoxifen. So, this trial compared giredestrant against the standard.
Jamie DePolo: And then, can you summarize the results for us? It sounded like they were very positive.
Dr. Aditya Bardia: That's exactly correct. The study met its primary endpoint. There was improvement in invasive disease-free survival. That was both statistically significant as well as clinically meaningful, with a hazard ratio of 0.70, so that's a 30% reduction in the risk of recurrence or death with the use of giredestrant over standard of care endocrine therapy.
Jamie DePolo:Okay, and let's talk about side effects, because both tamoxifen and the aromatase inhibitors have side effects. We know that, roughly, about 50% of people stop taking them early. I guess I'm wondering if you could talk about the side effects, and then also would giredestrant be prescribed for 5 to 10 years, like the aromatase inhibitors are?
Dr. Aditya Bardia: Absolutely. In the clinical trial, patients were allowed to continue with giredestrant beyond five years. We've not hit that mark yet in the clinical trial, but that is allowed per protocol, and absolutely, for patients with high-risk disease, we tend to consider seven to 10 years of adjuvant endocrine therapy, so you want an agent that's better tolerated.
Jamie DePolo: And the side effects, I think, were similar for giredestrant with AIs and tamoxifen, but there were a couple differences?
Dr. Aditya Bardia: That's exactly correct. So, overall, the frequency of AEs [adverse effects] were similar, including the frequency of arthralgias with giredestrant as with the standard of care endocrine therapy, but treatment discontinuation because of arthralgia was lower with giredestrant as compared to standard of care endocrine therapy.
Jamie DePolo: And just for everybody who doesn't know, arthralgia, that's joint pain, correct?
Dr. Aditya Bardia: That's exactly correct. Muscle aches and joint aches.
Jamie DePolo: And so, what do these results mean for people with early-stage hormone receptor-positive disease? And then I'm also wondering...you talked a little bit about it in your presentation. What about the CDK4/6 inhibitors? How does giredestrant fit in with that?
Dr. Aditya Bardia: Absolutely. So, the study met its primary endpoint. It's not FDA-approved at this time, but in the future, if it's approved, then that could be an option for patients with stage I to stage III ER-positive HER2-negative early breast cancer, and in terms of combination that is ongoing, giredestrant is being combined with abemaciclib for patients with ER-positive HER2-negative breast cancer. So, combination data is also being generated in the early breast cancer setting.
Jamie DePolo: Dr. Bardia, thank you so much. Appreciate your time.
Dr. Aditya Bardia: Absolutely. Thanks for having me.
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