Dr Tolaney on the Design of the ELEGANT Trial in ER+, HER2-Negative Early Breast Cancer

“I think of this as a sequential study, meaning that it's not using the oral SERD upfront, but rather waiting until [the patients have] gotten through that initial high-risk period and then randomly assigning them to the SERD or continuation of endocrine treatment.”

Sara M. Tolaney, MD, MPH, chief of the Division of Breast Oncology and associate director the Susan F. Smith Center for Women’s Cancers, as well as a senior physician at Dana-Farber Cancer Institute; and an associate professor of medicine at Harvard Medical School, discussed the potential clinical significance of the ongoing phase 3 ELEGANT trial (NCT06492616), which is investigating elacestrant (Orserdu) vs standard endocrine therapy in patients with estrogen receptor (ER)–positive, HER2-negative early breast cancer with high risk of recurrence.

The ELEGANT study population includes high-risk patients with ER-positive breast cancer, and the enrollment criteria are similar to those that were used in the phase 3 monarchE trial (NCT03155997) of abemaciclib (Verzenio) plus endocrine therapy, Tolaney began. Notably, patients enrolled in ELEGANT must have completed 2 to 5 years of systemic therapy.

The ELEGANT study is designed as a sequential trial, meaning the oral selective estrogen receptor degrader (SERD) elacestrant is administered after the initial high-risk treatment period, rather than upfront, according to Tolaney. Patients will be randomly assigned to receive either elacestrant or endocrine therapy of the physician’s choice. The primary end point for this trial is invasive breast cancer–free survival, with the goal of demonstrating the ability to prevent recurrences in this high-risk group, Tolaney explained.

The ELEGANT study is not entirely unique, as several other oral SERDs are in development within the early breast cancer setting, Tolaney contextualized. Two other trials in this setting for patients who have completed 2 to 5 years of prior treatment are the phase 3 CAMBRIA-1 (NCT05774951) and EMBER-4 (NCT05514054) studies. CAMBRIA-1 is randomly assigning patients to receive camizestrant or endocrine therapy, and EMBER-4 is investigating imlunestrant (Inluriyo) vs endocrine therapy.

There are key distinctions between the eligibility criteria of these trials, Tolaney emphasized. ELEGANT focuses exclusively on the highest-risk patients and is not enrolling node-negative patients with high-risk features. Conversely, CAMBRIA-1 is enrolling patients with intermediate- or high-risk disease, and EMBER-4 is enrolling those with disease at higher-than-average risk of recurrence. Furthermore, the CAMBRIA-1 and EMBER-4 trials are nearing completion of accrual, whereas ELEGANT will remain open, providing an ongoing option for patient enrollment in this setting, Tolaney concluded.