Both the primary and key secondary end point of the phase 3 EMERALD study have been reached.
Treatment with single-agent elacestrant improved progression-free (PFS) and overall survival (OS) compared with standard of care (SOC) in patients with estrogen receptor (ER)-positive, HER2-negative advanced or metastatic breast cancer (mBC), meeting the primary end point and 1 secondary end point of the phase 3 EMERALD study, according to topline results announced in a press release from Radius Health, Inc.1
EMERALD is a randomized, open-label, active-controlled trial (NCT03778931) of elacestrant–a selective ER degrader (SERD) administered as a once-daily oral treatment–as a second- and third-line treatment of patients with ER-positive, HER2-negative advanced mBC. In addition to PFS and OS, the study is also evaluating the objective response rate (ORR) and duration of response (DOR) to elacestrant treatment.
“Advanced/metastatic ER-positive/HER2-negative BC pre-treated with endocrine therapy remains an area of high unmet medical need. Additional therapeutic options for this patient population are urgently needed,” said principal investigator Aditya Bardia, MD, MPH, a medical oncologist at Massachusetts General Hospital and assistant professor of medicine at Harvard Medical School, in the release. “The trial results being statistically significant demonstrate a standard clinically meaningful improvement of PFS in the elacestrant group versus endocrine of care in patients previously treated with endocrine therapies and CDK 4/6 inhibitors. The results provide a significant advancement for patients suffering from this devastating disease. It was also important to see the positive data for those patients with ESR1 mutations, known to confer additional resistance to standard endocrine therapy.”
In the study, investigators enrolled approximately 466 patients who were randomly assigned to receive oral elacestrant 400 mg daily or the investigator’s choice of SOC therapy of either fulvestrant 500 mg administered intramuscularly, anastrozole 1 mg/day, letrozole 2.5 mg/day, or exemestane 25 mg/day on a continuous dosing schedule. Of those enrolled, 47% harbored an ESR1 mutation.2
Patients were eligible to enroll in the study given they were 18 years of age or older with a diagnosis of breast adenocarcinoma with measurable disease or non-measurable bone-only disease, ER-positive tumor status, and HER2-negative tumor status who were candidates for endocrine therapy. Patients were required to have received between 1 to 2 lines of endocrine therapy for advanced or mBC, a CDK 4/6 inhibitor in combination with fulvestrant or an aromatase inhibitor, 1 or more lines of chemotherapy in the advanced/metastatic setting, and ESR1 mutant or wildtype disease in according to circulating tumor DNA.
The study excluded patients who were previously treated with elacestrant or other investigational SERD or ER antagonists. Prior anticancer or investigation treatment with fulvestrant within 28 days of enrolling, endocrine therapy within 14 days, chemotherapy within 21 days, or another investigational anticancer therapy within 28 days. Patients with the presence of visceral disease were also ineligible for the study.
“We are extremely excited as elacestrant is the first oral SERD to show positive topline results in a pivotal trial as a monotherapy vs SOC for the treatment of ER-positive HER2-advanced or mBC,” commented Elcin Barker Ergun, chief executive officer of the Menarini Group, in the press release.1 “The results pave the way towards our working with the regulators to bring elacestrant to patients with ER-positive/HER2-negative advanced or metastatic breast cancer, which remains a huge unmet medical need. Notably, the topline results were also positive for the ESR1 mutation sub-segment, an important driver of resistance to endocrine therapy in ER-positive/HER2-negative mBC patients.”
Investigators continue to evaluate data from the EMERALD trial. Full results from the study will be presented in December 2021 at the San Antonio Breast Cancer Symposium.
1. Menarini Group and Radius Health announce positive phase 3 topline results from the EMERALD trial evaluating elacestrant in breast cancer. News release. October 20, 2021. Accessed October 21, 2021. https://bit.ly/3aVzTW1
2. Phase 3 trial of elacestrant vs. standard of care for the treatment of patients with ER+/HER2- advanced breast cancer (EMERALD). Clinicaltrials.gov. Accessed October 21, 2021. https://bit.ly/3aVzTW1