In this conference update video, Profs. Shaheenah Dawood, Heather McArthur, Javier Cortés, and Frédérique Penault-Llorca provide key insights from the highly anticipated 13thAsia-Pacific Breast Cancer Summit (APBCS) Satellite Symposium, sponsored by Menarini Stemline.
The esteemed faculty discusses treatment strategies and sequencing options after ET + CDK4/6i for patients with ER+/HER2- metastatic breast cancer (mBC).
Topics of discussion include:
- Overview of the ESMO mBC living guidelines
- Overcoming endocrine resistance after 1st line ET+CDK4/6i (intrinsic & acquired)
- The benefit of biomarker-selected endocrine-based therapies in ER+/HER2- mBC
- ESR1 mutation: clinical significance and testing strategies
Clinical takeaways
- ET + CDK4/6i remains the SOC for 1st line treatment in ER+/HER2- mBC. Guidelines recommend exhausting sequential ET-based regimens in the 2nd line setting (as monotherapy or combinations).
- The challenge of treating ER+/HER2− BC after 1st line ET+CDK4/6i is to overcome endocrine resistance. Molecular resistance patterns include intrinsic alterations and acquired resistance mechanisms (e.g. ESR1-mut).
- Elacestrant provides clinically meaningful improvements in PFS for patients with ER+/HER2- mBC who received at least 12 months of ET+CDK4/6i in 1st line and whose tumours harbour ESR1-mut. This benefit was consistent across clinically relevant subgroups.
- Safety analyses demonstrated that elacestrant had a manageable safety profile similar to other ETs and without evidence of some of the toxicities associated with other drug classes, such as CDK4/6i and PI3K/AKT/mTOR inhibitors.
- ESR1-mut testing should be done at 1st line progression via liquid biopsy due to disease subclonality; if negative, repeat at each progression. Archival tissue should not be used for testing due to the acquired nature of ESR1-mut.