The future of ER+/HER2-mBC treatment

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Dr. Bardia provides insight into the current state of the ER+/HER2- treatment landscape and the place of elacestrant in the current treatment paradigm.

Dr. Aditya Bardia: Based on the results of the EMERALD trial, Elacestrant could potentially be used as a second line for patients with ER-positive HER2-negative metastatic breast cancer. The EMERALD trial was in monotherapy. There is also interest in combination therapy combining endocrine agents with other targeted agents such as PI3 kinase inhibitors as well as everolimus, which would also be of interest.

Aromatase inhibitors are currently used in the adjuvant setting for patients with early postmenopausal breast cancer and they are also used in the metastatic setting as first-line therapy in combination with a CDK4/6 inhibitor . In terms of second, third line, we sometimes use aromatase inhibitors in combination with everolimus, so if Elacestrant is approved by the FDA as a second, third line, some doctors would consider using it as single agent, but there are others who would be interested in combination therapy in combination with an mTOR PI3 kinase or other targeted agents.

In terms of unmet needs for patients with ER-positive, HER2-negative breast cancer, I can highlight three. The first is that we need better endocrine agents. For example, fulvestrant is a selective estrogen receptor degrader, but is administered by intramuscular injection, which may be inconvenient for female patients. We therefore need oral options for patients with ER-positive HER2-negative metastatic breast cancer. The second unmet need is that once patients have endocrine-resistant disease, the mainstay of management is currently chemotherapy. Their interest in antibody-drug conjugates, trastuzumab deruxtecan, sacituzumab govitecan, but we need better agents that can help prolong the survival of patients with ER-positive metastatic breast cancer and also improve the quality of life in this context. Finally, the unmet need is to prevent ER-positive metastatic breast cancer. If we have good therapies for early breast cancer, if we can diagnose breast cancer early, we can potentially prevent the emergence of metastatic disease, which would be great for our patients.

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