SABCS 2024: The Role of ESR1 Mutation Testing and Combination Strategies in Metastatic HR+/HER2- Breast Cancer

In an interview with Pharmacy Times®, Virginia Kaklamani, MD, DSc, professor of medicine in the Division of Hematology-Medical Oncology at The University of Texas Health Science Center San Antonio, discussed real-world data that confirms the benefit of elacestrant in patients with metastatic HR+/HER2- breast cancer harboring ESR1 mutations, demonstrating a robust median progression free survival (PFS) of over 8 months. Kaklamani shared that combinations of elacestrant with other targeted therapies like abemaciclib and mTOR inhibitors are being explored and show promise. ESR1 mutation testing, particularly through liquid biopsies, is crucial to identify patients who may benefit most from elacestrant and other oral endocrine therapies. Ongoing clinical trials are studying larger cohorts to determine the optimal combination strategies with elacestrant.

Pharmacy Times

What are the key findings from the real-world analysis of OR-SER-DU in ER+/HER2- advanced breast cancer?

Virginia Kaklamani, MD, DSc

So, the real-world data confirmed the benefit of elacestrant in patients that have metastatic HR+/HER2- breast cancer with tumors that have ESR1 mutation, so in a robust medium PFS of more than 8 months.

Pharmacy Times

What are the potential benefits of combining elacestrant with abemaciclib in ER+/HER2- metastatic breast cancer?

Kaklamani

So, we have a lot of endocrine therapies. We have a lot of other targeted therapies, and we're trying to find the best way to give them, and sometimes the best ways to combine them with each other. So, the combination of abemaciclib and elacestrant has been shown to be effective. It also is well tolerated. There are also other combinations with elacestrant and mTOR inhibitors, such as everolimus, alpelisib and so forth, that also have a lot of promise. Trials are ongoing. There's going to be larger cohorts that we're going to be studying, and hopefully, with those results, we'll find the sweet spot of how to give elacestrant best.

Pharmacy Times

What is the continued need for ESR1 testing in clinical practice, and how might this impact treatment decision-making?

Kaklamani

ESR1 mutation testing is extremely important. This is how we will know whether we can give elacestrant and other oral SERDS or not. We know that these SERDS are more effective in patients that have tumors with ESR-1 mutations. So how do we test for ESR-1 mutations? We're going to test in the liquid. The best way to find ESR-1 mutations is in liquid biopsies, and it's in patients that have previously been exposed to endocrine therapy. If we test at the primary site and the primary tumor, we're likely not going to find an ESR-1 mutation. Even if we test the tumor and the first metastatic site, we're not going to find ESR-1 mutations very often. Where we find them is when the tumor has been exposed to endocrine therapy over and over again.