First Oral SERD Elacestrant Achieves Positive Findings in EMERALD Trial for ER+/HER2– Advanced or Metastatic Breast Cancer

The selective estrogen receptor degrader (SERD) elacestrant (RAD-1901) yielded positive outcomes in a population of patients with estrogen receptor–positive, HER2-negative advanced or metastatic breast cancer, according to a press release from the drug’s developer Radius Health.

The treatment was assessed as part of the pivotal phase 3 EMERALD trial (NCT03778931) in which the oral SERD yielded positive topline data compared with standard of care. Both primary end points of the trial were met, including progression-free survival (PFS) in the overall patient population and in those with an ESR1 mutation. Both end points proved to be statistically significantly in favor of the elacestrant arm.

In light of these results, the Menarini Group and Radius Health plan on proceeding with regulatory submissions to both the FDA and the European Union’s EMA in 2022. Results from the trial will be presented at the upcoming San Antonio Breast Cancer Symposium in December 2021.

“Advanced /metastatic ER+/HER2– [breast cancer] pre-treated with endocrine therapy remains an area of high unmet medical need. Additional therapeutic options for this patient population are urgently needed,” Aditya Bardia, MD, MPH, a medical oncologist at the Massachusetts General Hospital, an associate professor in the Medicine Department at Harvard Medical School, and principal investigator for the EMERALD trial, said in a statement.

“The trial results being statistically significant demonstrate a clinically meaningful improvement of PFS in the elacestrant group versus endocrine standard 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.”

Investigators enrolled 466 patients on the EMERALD study, 47% of whom (n = 220) had tumors harboring an ESR1 mutation. Patients in the experimental arm were treated with 400 mg of elacestrant per day and the control arm was given 1 of several standard of care therapies: 500 mg of intramuscular fulvestrant as 2 5 mL injection doses on day 1 and 15 of cycle 1 and day 1 of every subsequent 28-day cycle, 1 mg of anastrozole per day, 2.5 mg of letrozole per day, and 25 mg of exemestane per day.

Secondary end point for the trial included overall survival in the ESR1-mutant and ESR1–wild type populations.

Notably, safety findings for elacestrant were consistent with previous clinical findings.

“Completing the EMERALD trial was a tremendous effort given the myriad of COVID-related obstacles across the globe. Our collective teams did an outstanding job delivering the results of the trial in a high-quality and, ultimately, successful manner. The Menarini Group and its leadership team are terrific partners. All of us at Radius look forward to supporting them through U.S. [new drug application] submission,” Kelly Martin, chief executive officer at Radius Health, concluded.

Reference

Menarini Group and Radius Health announce positive phase 3 topline results from the EMERALD trial evaluating elacestrant in breast cancer. News release. Radius Health. October 20, 2021. Accessed October 21, 2021. https://bit.ly/3b4VMlv