Chemotherapy and Targeted Therapy for Endocrine-Pretreated or Hormone Receptor–Negative Metastatic Breast Cancer Rapid Recommendation Update

Dr. Beverly Moy is back on the ASCO Guidelines Podcast to discuss the latest guideline rapid recommendation update regarding sacituzumab govitecan for patients with hormone receptor-positive HER2-negative metastatic breast cancer based on recent evidence published in TROPiCS-02. Dr. Moy reviews how this update intersects with the previous rapid recommendation update on trastuzumab deruxtecan and future areas of research that may impact further updates to this evidence-based guideline. Read the latest update, "Chemotherapy and Targeted Therapy for Endocrine-Pretreated or Hormone Receptor–Negative Metastatic Breast Cancer: ASCO Guideline Rapid Recommendation Update" at www.asco.org/breast-cancer-guidelines. TRANSCRIPT Brittany Harvey: Hello and welcome to the ASCO Guidelines podcast, one of ASCO's podcasts delivering timely information to keep you up to date on the latest changes, challenges, and advances in oncology. You can find all the shows, including this one at asco.org/podcasts.   My name is Brittany Harvey and today I'm interviewing Dr. Beverly Moy from Massachusetts General Hospital in Boston, Massachusetts, lead author on ‘Chemotherapy and Targeted Therapy for Endocrine-Pretreated or Hormone Receptor–Negative Metastatic Breast Cancer: ASCO Guideline Rapid Recommendation Update’. Thank you for being here, Dr. Moy. Dr. Beverly Moy: Thank you for having me, Brittany. I'm glad to be here. Brittany Harvey: Then first, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The full conflict of interest information for this guideline panel is available in line with the publication of the guideline in the Journal of Clinical Oncology. Dr. Moy, do you have any relevant disclosures that are directly related to this guideline topic? Dr. Beverly Moy: I do not have any relevant disclosures. Brittany Harvey: It's great to have you back on the podcast. Last we spoke, we were discussing the July 2022 rapid update of this guideline regarding the use of trastuzumab deruxtecan. What prompted the second rapid update to the guideline? Dr. Beverly Moy: Thank you very much for that question, Brittany. The guidelines committee decided to issue another rapid guideline update because of the second interim analysis results of the TROPiCS-02 trial. This trial showed that sacituzumab govitecan had a significant improvement of over three months in overall survival compared to chemotherapy of physician’s choice in patients with pretreated metastatic hormone receptor positive and HER2/neu-negative breast cancer. So we felt that the strength of this data compelled the ASCO guideline ommittee to issue yet another update. Brittany Harvey: Understood. So then, based off this strong data that you just mentioned from TROPiCS-02, what is the updated recommendation from the guideline expert panel? Dr. Beverly Moy: So the guidelines expert panel really wanted to get this information out because we felt compelled that clinicians should be aware that sacituzumab govitecan is another treatment option for patients with endocrine-resistant metastatic hormone receptor- positive and HER2-negative breast cancer. So we felt that clinicians may use this drug in patients who have received at least two prior treatments in a metastatic setting. Brittany Harvey: Okay, you just mentioned this is one of several treatment options. So as this new recommendation is implemented, what should clinicians know? Dr. Beverly Moy: So, I think that clinicians really need to be aware that sacituzumab govitecan, which is a newer drug, as an antibody drug conjugate, it really does have a role in patients with metastatic hormone receptor positive, HER2/neu-negative endocrine-refractory breast cancer. I think clinicians have been used to this drug in the setting of metastatic triple-negative breast cancer, but the results of theTROPiCS-02 trial would show us that it actually has a lot of efficacy and even an overall survival benefit in patients with metastatic hormone receptor-positive breast cancer. So clinicians should be made aware that this is a treatment option that does give an overall survival benefit. Brittany Harvey: Great. It's great to hear that there's an overall survival benefit with this drug. So, in addition to that, how does this rapid update impact patients with hormone receptor-positive HER2-negative metastatic breast cancer? Dr. Beverly Moy: So I think that it's important for clinicians to remember that patients with metastatic hormone receptor-positive HER2/neu-negative breast cancer, the first-line therapies are endocrine therapy and targeted therapies. But when their disease becomes endocrine refractory, we have several treatment options, and usually the standard is sequential single-agent chemotherapy. What this guideline update is telling us is that sacituzumab govitecan, when compared to other treatments of physician’s choice, really does improve overall survival and progression-free survival. So it really should be considered. Brittany Harvey:  Excellent. And then finally, are there ongoing research developments that the panel is keeping an eye on for any future updates to this guideline? I know this guideline was last published in 2021 and there's already been two rapid updates to it. Dr. Beverly Moy: Yes, that's a really great question, Brittany, because this is a very active field, and I think that it's important actually to take this guideline update with sacituzumab govitecan in the context of our last guideline update, which, as you said earlier, was with the other antibody drug conjugate trastuzumab deruxtecan. That was our last guideline update in patients who had what we call metastatic HER2 low disease, where trastuzumab deruxtecan had a significant overall survival advantage as well. So what these two guideline updates are really pointing out is that there's this new class of drugs, these antibody drug conjugates, that have so much promise and so much activity in metastatic breast cancer, whether it's hormone receptor-positive or hormone receptor-negative. So future research really has to help us clarify how do we sequence these drugs most appropriately now that we have these two very active treatment options that have a significant overall survival advantage. And then research also has to really guide us into the resistance mechanisms that may be in common or not in common with these two antibody drug conjugates. So I think that we're really looking at results of future trials to see how best to sequence them, if they should be used earlier in treatment in the metastatic setting, and we await the results of those trials. Brittany Harvey: Absolutely. We'll look forward to those future research developments and work with you and the panel to continuously update these guidelines. So I want to thank you so much for your work leading these guideline rapid recommendation updates, and thank you for your time today, Dr. Moy. Dr. Beverly Moy: Thank you, Brittany, for having me. Brittany Harvey: And thank you to all our listeners for tuning in to the ASCO Guidelines podcast series. To read the full guideline, go to www.asco.org/breast-cancer-guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app available in the Apple App Store or the Google Play Store. 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