Dr Bardia on the Investigation of Elacestrant vs Endocrine Therapy in ER+ Early Breast Cancer

“Can we move elacestrant to [the setting of] early breast cancer, where the majority of patients are treated, [so] they can have access to this therapy?”

Aditya Bardia, MD, MPH, FASCO, a professor in the Department of Medicine in the Division of Hematology/Oncology, the director of Translational Research Integration, and a member of Signal Transduction and Therapeutics at the UCLA Health Jonsson Comprehensive Cancer Center, discussed the unique design of the phase 3 ELEGANT study (NCT06492616), which is evaluating elacestrant (Orserdu) vs endocrine therapy in patients with estrogen receptor (ER)–positive, HER2-negative early breast cancer at high risk of recurrence.

Although elacestrant is currently FDA approved for the management of ER-positive, HER2-negative, ESR1-mutated metastatic breast cancer, most patients with localized, ER-positive disease receive endocrine therapy as the mainstay of treatment, Bardia began. The objective of the ELEGANT study is to determine whether transitioning elacestrant into earlier stages of treatment can improve outcomes for this patient population, he said.

ELEGANT is a randomized trial designed to evaluate the efficacy of elacestrant compared with standard-of-care (SOC) endocrine therapy. Bardia noted that after evaluating several potential study designs, the study’s steering committee and sponsor opted for a switch strategy. Under this protocol, patients undergo an initial treatment period of 2 to 5 years of endocrine therapy. Following this window, eligible patients are randomly assigned to either continue to receive their current SOC endocrine therapy regimen or switch to elacestrant for the remainder of their treatment course.

The rationale for the switch design is multifaceted, accounting for both tumor biology and the evolving therapeutic paradigm, according to Bardia. Notably, the widespread FDA approval of CDK4/6 inhibitors for patients with early breast cancer—specifically abemaciclib (Verzenio) for a 2-year duration and ribociclib (Kisqali) for a 3-year duration has altered the standard treatment trajectory for high-risk patients during the first few years of therapy, he explained. Because the ELEGANT trial seeks to compare one endocrine monotherapy vs another, the study investigators determined that the most clinically appropriate placement for elacestrant would be following the completion of initial CDK4/6 inhibitor regimens, he reported. Consequently, the ELEGANT trial allows for prior exposure to CDK4/6 inhibitors, he concluded.