Ongoing Research and Unmet Needs in Patients With Breast Cancer and ESR1 Mutations

EP: 1.Testing for ESR1 Mutations in Breast Cancer

EP: 2.Overcoming Challenges in Biomarker Testing in Breast Cancer

EP: 3.PADA-1 Trial: ctDNA Monitoring for Acquired ESR1 Mutations in Advanced Breast Cancer

EP: 4.EMERALD: Elacestrant in ER+/HER2- Advanced Breast Cancer

EP: 5.The Role of Elacestrant in Breast Cancer

EP: 6.SERENA-2: Camizestrant vs Fulvestrant in Advanced ER+/HER2- Breast Cancer

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EP: 7.Ongoing Research and Unmet Needs in Patients With Breast Cancer and ESR1 Mutations

This is a synopsis of an Insights series featuring Kevin Kalinsky, MD, MS, of Winship Cancer Institute of Emory University, and Erica L. Mayer, MD, MPH, of Dana-Farber Cancer Institute.

As the discussion concluded, Dr Erica Mayer highlighted several promising novel agents for hormone receptor-positive breast cancer beyond selective estrogen receptor degraders [SERDs]. These include proteolysis-targeting chimeras [PROTACs] like ARV-471 [vepdegestrant] and selective estrogen receptor covalent antagonists [SERCAs] like H3B-6527 which may more potently inhibit estrogen receptor signaling.

Early phase clinical data presented at recent conferences suggests meaningful single-agent activity from both investigational drug classes despite heavily pretreated populations, with manageable toxicity. Combinations also appear feasible, though some unique drug-drug interactions may require consideration, as Dr Kevin Kalinsky noted a PROTAC/CDK4/6 inhibitor regimen showed heightened neutropenia.

Dr Kalinsky was also intrigued by phase III results for the selective estrogen receptor modulator lasofoxifene from the ELAINE studies, which improved progression-free survival over endocrine options when combined with abemaciclib. The ongoing phase III ELAINE-3 trial is evaluating lasofoxifene plus abemaciclib compared with fulvestrant plus abemaciclib specifically in patients harboring ESR1 mutations who progressed on prior CDK4/6 blockade. Demonstrating efficacy in this post-CDK4/6 setting could support a differentiated approval.

In closing, Dr Mayer emphasized practical challenges to integrating comprehensive genomic profiling for targetable alterations like ESR1 mutations into real-world practice. Overcoming barriers to accessible, serial ctDNA testing is imperative to realize the full potential of emerging biomarker-driven breast cancer therapies. Drs Kalinsky and Mayer urge focused education and implementation efforts surrounding ctDNA analysis to evolve the standard of care.

*Video synopsis is AI-generated and reviewed by OncLive editorial staff.