FDA Approval Sought for Elacestrant in ER+/HER2- Breast Cancer

A new drug application has been submitted to the FDA seeking the approval of elacestrant in the treatment of patients with estrogen receptor–positive, HER2-negative, advanced or metastatic breast cancer.

A new drug application has been submitted to the FDA seeking the approval of elacestrant in the treatment of patients with estrogen receptor (ER)–positive, HER2-negative, advanced or metastatic breast cancer.1

The application is supported by data from the phase 3 EMERALD trial (NCT03778931). At a median follow-up of 15.5 months, the oral selective estrogen receptor degrader (SERD; n = 239) was found to reduce the risk of disease progression by 30% compared with standard-of-care (SOC; n = 238) treatment per blinded independent central review (BICR; HR, 0.70; 95% CI, 0.55-0.88; P = .0018).2 The median progression-free survival (PFS) in the investigative arm was 2.8 months vs 1.9 months in the control arm.

Moreover, a landmark analysis revealed that the 6-month PFS rate with elacestrant was 34.3% (95% CI, 27.2%-41.5%) vs 20.4% (95% CI, 14.1%-26.7%) with SOC. The 12-month PFS rates in the investigative and control arms were 22.3% (95% CI, 15.2%-29.4%) and 9.4% (95% CI, 4.0%-14.8%), respectively.

Additionally, 228 patients had detectable ESR1 mutations at baseline; 115 of these patients received elacestrant, and 113 were given SOC. In this population, the hazard ratio for PFS was 0.55 (95% CI, 0.39-0.77; P = .0005) favoring elacestrant. The median PFS with the SERD was 3.8 months vs 1.9 months with SOC. Moreover, the 6-month PFS rates in the investigative and control arms were 40.8% (95% CI, 30.1%-51.4%) and 19.1% (95% CI, 10.5%-27.8%), respectively; the 12-month rates were 26.8% (95% CI, 16.2%-37.4%) and 8.2% (95% CI, 1.3%-15.1%), respectively.

“We are excited about the potential for elacestrant to be approved for treatment of patients with advanced or metastatic ER-positive/HER2-negative breast cancer, which constitutes about 70% of breast cancer and remains an area of significant unmet medical need,” Elcin Barker Egun, chief executive officer of The Menarini Group, stated in a press release. “Elacestrant has shown statistically significant efficacy over current SOC medications both for overall population and in patients whose tumors harbor an ESR1 mutation, one of the most difficult-to-treat mechanisms of acquired resistance that develops in the later stages of metastatic/advanced breast cancer.”

EMERALD enrolled patients with advanced or metastatic breast cancer who had ER-positive and HER2-negative disease. To be eligible, they were required to have progressed or relapsed on or following 1 or 2 lines of endocrine therapy for advanced disease, one of which given in combination with a CDK4/6 inhibitor. They also needed to have received at least 1 line of chemotherapy for advanced disease, and an ECOG performance status of 0 or 1.

A total of 477 study participants were randomized 1:1 to receive elacestrant at 400 mg daily vs investigator’s choice of fulvestrant, anastrozole, letrozole, or exemestane (SOC). SOC guidance recommended use of a different endocrine therapy than what had previously been received. Key stratification factors included ESR1 mutational status (yes vs no), prior fulvestrant (Faslodex) treatment (yes vs no), and presence of visceral metastases (yes vs no).

The co-primary end points of the trial were PFS in all patients and in the subgroup of patients with ESR1-mutated tumors. Key secondary end points included overall survival (OS) in both populations. Other secondary end points were PFS and OS in those without ESR1 mutations, PFS per investigator assessment, overall response rate, duration of response, and clinical benefit rate, as well as safety and tolerability.

Baseline patient characteristics were well balanced in the overall patient population. The median age was 63 years (range, 24-89) in the investigative arm vs 64 years (range, 32-83) in the control arm. Most patients had visceral metastases (68.2% vs 71%, respectively), previous adjuvant therapy (66.1% vs 59.2%), and had not received chemotherapy in the advanced or metastatic setting (79.9% vs 75.6%).2

Previous endocrine treatment received by those in the elacestrant arm included fulvestrant (29.3%), an aromatase inhibitor (AI; 80.8%), and tamoxifen (7.9%). In the SOC arm, 31.5% received prior fulvestrant, 81.8% previously received an AI, and 6.3% received prior tamoxifen.

Additional data from subgroup analyses showed that in those who did not receive prior chemotherapy (n = 371), the median PFS with elacestrant (n = 191) was 3.68 months (95% CI, 2.33-5.49) vs 1.97 (95% CI, 1.87-3.55) with SOC (n = 190; HR, 0.681; 95% CI, 0.520-0.891; P = .00388).3 In all patients who did not receive prior chemotherapy (n = 323), the PFS was significant improved with the SERD (n = 191) vs fulvestrant (n = 132), at a median of 3.68 months (95% CI, 2.33-5.49) and 1.97 months (95% CI, 1.87-3.68), respectively (HR, 0.636; 95% CI, 0.465-0.868; P = .0032).

In the subset of patients with ESR1-mutated disease who did not previously receive chemotherapy (n = 170), the median PFS was 5.32 months (95% CI, 3.65-9.03) with elacestrant (n = 89) vs 1.91 months (95% CI, 1.87-3.71) with SOC (n = 81; HR, 0.535; 95% CI, 0.356-0.799; P = .00235). In those with ESR1-mutated disease who did not previously receive chemotherapy (n = 153), PFS was significantly improved with the SERD (n = 89) vs fulvestrant (n = 64), at 5.32 months (95% CI, 3.65-9.03) and 1.91 months (95% CI, 1.87-3.68), respectively (HR, 0.487; 95% CI, 0.310-0.761; P = .005).

Elacestrant was found to have a manageable safety profile that is consistent with other endocrine therapies. Key treatment-related toxicities experienced by those who received elacestrant and had no prior chemotherapy were nausea (25.9%), fatigue (12.7%), and hot flush (11.1%). Notably, no treatment-related deaths occurred in either treatment arm.

A marketing application for elacestrant in the European Union is anticipated to be filed in the second half of 2022.


  1. Menarini Group and Radius Health submit new drug application to the US FDA for elacestrant. News release. The Menarini Group and Radius Health, Inc. June 22, 2022. Accessed June 23, 2022. https://bit.ly/3bplt3F
  2. Bidard F-C, Kaklamani VG, Neven P, et al. Elacestrant (oral selective estrogen receptor degrader) versus standard endocrine therapy for estrogen receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer: results from the randomized phase III EMERALD trial. J Clin Oncol. Published online May 18, 2022. doi:10.1200/JCO.22.00338
  3. Kaklamani V, Bardia A, Aftimos P, et al. Subgroup analysis of patients with no prior chemotherapy in EMERALD: a phase 3 trial evaluating elacestrant, an oral selective estrogen receptor degrader (SERD), versus investigator’s choice of endocrine monotherapy for ER+/HER2- advanced/metastatic breast cancer (mBC). J Clin Oncol. 2022;40(suppl 16):1100. doi:10.1200/JCO.2022.40.16_suppl.1100