Evolution in the Field of HR+ Breast Cancer Management

Transcript:

Aditya Bardia, MD, MPH: For the last section, [we’ll look at] what’s exciting in the space of ER [estrogen receptor]–positive metastatic breast cancer in terms of drugs and biomarkers. Let’s start with you, Heather. What are you excited about over the next few years in terms of new developments in ER+ metastatic breast cancer?

Heather McArthur, MD: It’s exciting that we have all these hormone therapy–based agents and oral drugs that are effective and that are improving survival and meaningful outcomes on clinical trials that patients and providers care about deeply. We mentioned avelumab. That’s the first time I’ve been excited about immunotherapy for hormone receptor [HR]–positive disease. Of course, there are neoadjuvant studies, phase 3, ongoing looking at immunotherapy combinations with chemotherapy. It will be interesting to see if that story continues.

We’re very excited about ADCs [antibody-drug conjugates] in HER2 [human epidermal growth factor receptor 2]–low ER+ disease…. That’s all very exciting, and I look forward to the technology with those ADCs improving on efficacy and mitigating toxicity that are often coupled with successful drug developments. As a sidebar—it’s not a therapeutic innovation, but it’s worth mentioning in the context of this disease—we’re talking about advanced disease today, but there was a positive study in pregnancy. It was exciting to see that patients can get pregnant and take a break from their endocrine therapy and then resume without incurring additional risk of developing metastatic hormone receptor–positive disease. There’s a lot of innovation to be excited about now.

Aditya Bardia, MD, MPH: There was certainly positive news coming out of San Antonio Breast Cancer Symposium [SABCS]. Sara, what are your thoughts about exciting innovations over the next 5 years?

Sara A. Hurvitz, MD: I want to underscore what Virginia said. The postMONARCH study is an important phase 3 study. It will provide further evidence of whether it’s beneficial for us to switch to a different CDK4/6 inhibitor. That’s going to be an important trial for us to look to. We’re all incredibly impressed with trastuzumab deruxtecan and targeting HER2 low in this space, as well as sacituzumab govitecan in hormone receptor–positive breast cancer for patients requiring chemotherapy. I’m super excited about the data relating to capivasertib, as well as all the data on estrogen receptor degraders.

I’m looking to the combination studies of SERDs [selective estrogen receptor degraders] and PROTAC in combination with CDK4/6 inhibitors. I’m also moving up to the early stage setting, where it’s going to be fascinating to see if SERDs provide benefit in a standard-design adjuvant study. Our data seem to indicate that these drugs are best in ESR1 mutations. That situation is rare early on in disease, but it will be interesting to see long-term data from those studies.

Aditya Bardia, MD, MPH: That’s exciting. Virginia, what are you excited about over the next few years? Maybe we’ll see additional data at SBCS in 2023. Will it be as good as 2022?

Virginia Kaklamani, MD: I’m sure we will. I’m waiting to see all these data. The sequencing of ADCs is going to be pivotal. We’re learning how to sequence the endocrine therapies, but how do we sequence the ADCs that we’re starting to use in this HR+ space? There’s something else. I’m taking a line from the book of Michelle, but we need to define endocrine resistance, at least molecularly. We have some clinical characteristics that we all play with, and that’s not perfect either. We probably need some work in the clinical setting as well. But how do we define endocrine resistance? Can we overcome it, or should we move on to chemotherapy and ADCs?

Aditya Bardia, MD, MPH: This is a good segue. Michelle, what are your thoughts on endocrine resistance and innovation related to this space in metastatic breast cancer?

S. Michelle Shiller, DO, AP/CP, MGP: I previously commented that every time we’re giving agents to these tumors, they’re going to change their molecular profile and background. I heard a lot of robust discussion looking at specifically like capivasertib, which is pending approval, and whether there’s a need to test for PIK3CA mutation any longer. It’s still important to gather those data and see what differences there may be based on the presence of that mutation but also others and how that may impact the response to therapy.

To be honest, I don’t have much background on the molecular characterization of hormone-resistant cancer. That’s something I’ll look at to see what they’re talking about in that space. Because I practice all tumor types, I’m constantly trying to keep up. We’re starting to use these tests to classify all kinds of tumors, like classifying melanomas and endometrial cancer. That’s something I can’t speak to for this topic. As we try to establish these with respect to endometrial cancer, as an example, we have some generic broad, sweeping categories, but most tumors don’t fit nicely into 1 category. We need to continue gathering the information so we can see how things separate individually and how that impacts clinical behavior and therefore treatment decisions.

Aditya Bardia, MD, MPH:That’s great. It’s exciting to see developments in precision therapeutics and precision diagnostics. I’m looking forward to these developments.

Transcript edited for clarity.