Novel Endocrine Agents for Patients With HR-Positive Breast Cancer

At the Great Debates and Updates in Women’s Oncology meeting, Seth Wander, MD, PhD, Massachusetts General Hospital, Boston, Massachusetts, participated in a debate on whether novel endocrine agents, such as proteolysis targeting chimera (PROTAC), complete estrogen receptor antagonist (CERAN), selective estrogen receptor modulators (SERM), and selective estrogen receptor covalent antagonist (SERCA), add anything different than selective estrogen receptor degraders (SERDs), for patients with hormone receptor (HR)-positive metastatic breast cancer

Dr Wander concluded, “The question of how we are going to integrate these drugs into our clinical practice, either as single agents or in combination, is really a rapidly evolving topic that's going to change a lot in the coming months and over the next couple of years.”

Transcript:

My name is Seth Wander and I'm a medical oncologist at the Massachusetts General Hospital in Boston. It's a pleasure to be with everybody today.

 [Michael] Danso [MD, Virginia Oncology Associates] and I just had a great debate and discussion about emerging anti-estrogen therapies for metastatic hormone receptor positive breast cancer. We were discussing oral SERDS in comparison to novel agents including SERMS, PROTAC, CERAN, and SERCA. We discussed a number of different factors.

I highlighted some of the preclinical data comparing these agents in the laboratory, suggesting that there might be some signs of differential activity and different cellular and xenograft models of breast cancer. And then we talked about a number of the emerging early phase and even later phase clinical trials looking at these agents, both as monotherapy and in combination with a number of different targeted agents.

We spent some time thinking about some of the molecular genomic factors that might influence which patients benefit the most, for example, from estrogen-directed monotherapy or from combination therapy with a CDK-inhibitor or a targeted inhibitor. 
Finally, we talked a little bit about some of the emerging toxicity data. All of these drugs in general have been really well tolerated, but we have seen some differences with unique toxicities related to specific agents compared to some of the other newer agents.

I think the question of how we're using these drugs in the clinic is obviously a moving target. At the moment, only the first of these agents have been approved based on the EMERALD study. We have elacestrant for ESR1-mutant patients that have progressed on prior anti-estrogen and CDK4/6 inhibitor therapy. The question of how are we going to integrate these drugs into our clinical practice, either as single agents or in combination, is really a rapidly evolving topic that's going to change a lot in the coming months and over the next couple of years.

I'm a big advocate for the idea of personalized oncology and the concept that we need to be monitoring patients with serial next-generation sequencing, typically via circulating tumor DNA to help identify mechanisms of resistance to anti-estrogens and to targeted therapies.

As we develop greater understanding of that information, we're going to be able to use it to help select therapies, specifically based on the mutational profile, which can change over time. This is a topic that we're going to be talking a lot about over the next couple of years.

Source:

Wander, S. “Novel Endocrine Agents: Do PROTAC, CERAN, SERM, SERVA Really Add Anything Different Than SERDs? — Yes.” Presented at Great Debates and Updates in Women’s Oncology. May 3-4, 2024; New York, NY.