Hope S. Rugo, MD, FASCO: Hello, and welcome to this OncLive Peer Exchange®: “Therapy Options in Hormone Receptor-Positive HER2 Negative Breast Cancer.” I'm Dr Hope Rugo, and I'm a breast medical oncologist at the University of California San Francisco's Comprehensive Cancer Center. I'm joined today by a panel of my colleagues who treat breast cancer. I'd like to welcome Dr Aditya Bardia, who's at Massachusetts General Hospital in Boston, Massachusetts; Dr Komal Jhaveri, who is at Memorial Sloan Kettering Cancer Center in New York City; Dr Mark Pegram from the Stanford Cancer Center at Stanford University in Palo Alto, California; and Dr Anne O'Dea from the University of Kansas Medical Center in Kansas City, Kansas. I think we have a nice geographic representation of experts in breast oncology in the United States. We're going to have an exciting discussion today talking about hormone and receptor-positive, HER2-negative breast cancer. Let's get started on our first topic. Komal will talk a little bit about outcomes in patients with hormone receptor-positive breast cancer and how this has changed over the last couple of decades.

Komal Jhaveri, MD, FACP: Thank you, Hope. We have come a very long way in the treatment of hormone receptor-positive disease. Certainly, when we even think about single-agent endocrine therapy, if we look at the current phase 3 trials in the first-line metastatic setting, we're seeing a difference in the overall survival. The gain that we've got in overall survival—it's nearly over 4 years even with single-agent endocrine therapy—but what has really been a big paradigm shift and a big revolutionary treatment paradigm now is the addition of CDK4/6 [cyclin-dependent kinases 4 and 6] inhibitors with an endocrine therapy. In more recent trials from CDK4/6, which have read out the overall survival gains, we're seeing that over 5 years. For example, in the MONALEESA-3 trial, which had 2 cohorts, including both first-line and second-line, the first line being the endocrine-sensitive patient population overall survival with the CDK4/6, and endocrine therapy was about 67 months. We're seeing progression-free survival gains with other targeted therapies—maybe alpelisib, which is the alpha-specific PI3K inhibitor in patients who harbor PIK3CA mutations; maybe with everolimus if we can use that. At this 2022 ASCO [American Society of Clinical Oncology] annual meeting, we heard the results for the DESTINY-Breast04 trial, antibody-drug conjugate, which has activity beyond HER2-positive disease and what we now define as HER2-low breast cancers, the majority of which are hormone receptor-positive disease. They have also had a progression via overall survival benefit—a lot of great gains.

Hope S. Rugo, MD, FASCO: It's an exciting time to hear about the advances we're making in this most common subset of breast cancer, the most common cancer worldwide in women. Maybe we've done a little bit better job at identifying our receptors, so that we can identify more about which patients are hormone receptor-positive. We heard today about additional testing looking at genomic signatures that might help further. Now we’ve heard about the CDK4/6 inhibitors from Komal. Of course, we're all using those, but, Anne, in your practice, how do you select and order therapy for a patient who has hormone receptor-positive, HER2-negative disease? We heard about how many options they have. How do you vary that based on menopausal status?

Anne O'Dea, MD: For me the most important thing I'm looking at is disease-free interval for these women. We're also looking at those patients that progress while receiving their adjuvant endocrine therapy. Of course, those patients have a much different biology than patients that have a 6-year or 7-year disease-free interval. Then we're selecting a first-line therapeutic option for them. I think that's the primary thing, and then we're looking at the patient's performance status. We're looking at their comorbid medical conditions, what their goals are, and certainly, volume of disease is a consideration as well. If you have a patient that has perhaps a single, solitary bone metastasis, that is very different from a patient that has visceral metastases. Those are sort of the things that I think through when I'm having this type of a discussion with a patient.

Hope S. Rugo, MD, FASCO: When you do think through those, do you always give a CDK4/6 inhibitor first-line? And then, how do you choose an AI [aromatase inhibitor]or fulvestrant as the partner?

Anne O'Dea, MD: The overwhelming totality of data that was described that really supports use of first-line CDK4/6. It's really a very rare patient in whom I'm not using that in the first line; perhaps an elderly patient in a skilled nursing facility where it's very cumbersome for her to have laboratory monitoring, or something like. However, outside of a situation like that, I’m really using it in all my patients. Typically, in terms of deciding aromatase inhibitor or fulvestrant, I'm really looking at that disease-free interval so those patients that are progressing on their adjuvant-AI, we're certainly going with fulvestrant for patients who have that very long disease-free interval. We're usually using an aromatase inhibitor.

Transcript edited for clarity.