Dr Callahan on the Potential Expansion of Oral SERD Use in ER+ Breast Cancer

“If there is an FDA approval of a combination of an oral SERD and a targeted agent, many of us would be excited to use [that regimen], and it would apply to a much broader patient population.”

Rena D. Callahan, MD, a breast medical oncologist at UCLA Health and an associate clinical professor of medicine at the David Geffen School of Medicine at UCLA, discussed the rapid evolution of systemic treatment protocols for patients with estrogen receptor (ER)–positive advanced breast cancer, focusing on the clinical utility and shifting paradigms of oral selective ER degraders (SERDs).

In her analysis of the current therapeutic paradigm, Callahan observed that although 2 oral SERDs—elacestrant (Orserdu) and imlunestrant (Inluriyo)—have received FDA approval, their use remains restricted to a specific subset of patients, with these indications currently limited to the treatment of patients with ER-positive, HER2-negative metastatic breast cancer harboring ESR1 mutations. Acquired ESR1 mutations in the ER typically occur after the tumor has been under the selective pressure of prior endocrine therapies, such as aromatase inhibitors, Callahan said.

She pointed out that the clinical reasoning behind these restrictive approvals is rooted in data from pivotal trials like the phase 3 EMERALD (NCT03778931) and EMBER-3 (NCT04975308) studies. These trials demonstrated that the primary benefit of using an oral SERD as a single agent was seen almost primarily in the populations of patients with disease harboring ESR1 mutations. Consequently, current standards of care necessitate identifying these mutations to justify the use of single-agent oral SERDs in a metastatic setting.

However, Callahan identified an emerging shift that could broaden the application of these therapies beyond the current mutation-restricted population. She noted that data from the phase 1/2 ELEVATE trial (NCT05563220), which is investigating elacestrant in combination with other targeted therapies in patients with metastatic breast cancer, indicate that the requirement for an ESR1 mutation may not be necessary for a patient to derive benefit when the SERD is part of a combination regimen. Callahan emphasized that if these combinations receive FDA approval, this would be a significant clinical advancement, allowing a much broader patient population to benefit from oral SERD–based treatments regardless of their mutation status.