Elacestrant was granted priority review by the FDA for the treatment of estrogen receptor–positive, HER2-negative metastatic breast cancer.
The FDA has granted priority review to the investigational selective estrogen receptor degrader elacestrant for patients with estrogen receptor (ER)–positive, HER2-negative metastatic breast cancer, according to a press release from the drugs’ developer The Menarini Group.1
Results from the phase 3 EMERALD trial (NCT03778931) helped to support the new drug application (NDA) in which the primary end points of progression-free survival (PFS) in the overall population and in the ESR1 mutation–positive population were improved when compared with standard of care (SOC) endocrine monotherapy.2 The Prescription Drug User Fee Act was set for February 17, 2023.
“The FDA’s acceptance of our NDA with priority review marks an important regulatory milestone for our company,” Elcin Barker Ergun, chief executive officer of the Menarini Group, said in the press release. “We look forward to working with the FDA during its review of this submission, which addresses a new potential therapeutic option for a major unmet need in the management of patients with advanced or metastatic breast cancer after resistance builds in the earlier lines of the treatment.”
According to results of the trial that were recently published in the Journal of Clinical Oncology, 477 patients were randomly enrolled with 239 patients receiving elacestrant and 238 receiving SOC. The median patient age was 63 years, and 47.8% of patients had the ESR1 mutation. Most patients had received either 1 (22.2%) or 2 (43.4%) prior lines of endocrine therapy. At the time of data cutoff, most patients had started (n = 466; 97.7%) and subsequently discontinued treatment (n = 442), with the median duration of follow-up being 15.1 months.
In the elacestrant arm, PFS was significantly longer compared with the SOC arm in the overall population (HR, 0.70; 95% CI, 0.55-0.88; P = .002) as well as in those with an ESR1 mutation (HR, 0.55; 95% CI, 0.39-0.77; P = .0005). At 6 months, the PFS rate with elacestrant in the overall trial population was 34.3% (95% CI, 27.2%-41.5%) vs 20.4% (95% CI, 14.1%-26.7%) in the SOC arm, with 12-month rates of 22.3% (95% CI, 15.2%-29.4%) and 9.4% (95% CI, 4.0%-14.8%), respectively. In those with an ESR1 mutation, 6-month PFS rates were 40.8% (95% CI, 30.1%-51.4%) versus 19.1% (95% CI, 10.5%-27.8%) with SOC, and 26.8% (95% CI, 16.2%-37.4%) and 8.2% (95% CI, 1.3%-15.1%), respectively, at 12 months.
At the interim analysis for overall survival, elacestrant resulted in better outcomes vs SOC in the overall (HR, 0.75; 95% CI, 0.54-1.04; P = .08) and ESR1 mutation–positive population (HR, 0.59; 95% CI, 0.36-0.96; P = .03).
The most common adverse effects (AEs) occurring in the elacestrant and SOC arms, respectively, were nausea (35.0% vs 18.8%), fatigue (19.0%-18.8%), vomiting (19.0% vs 8.3%), decreased appetite (14.8% vs 9.2%), and arthralgia (14.3% vs 16.2%). In the elacestrant arm, the most common grade 3/4 AEs were nausea (2.5%), back pain (2.5%), and increased alternative lengthening (ALT) telomeres (2.1%) with lower rates of grade 3/4 nausea (0.9%), fatigue (0.9%), diarrhea (0.9%), and aspartate aminotransferase (0.9%) occurred in the SOC group. Treatment discontinuation occurred in 6.3% of patients in the elacestrant arm and 4.4% in the SOC arm.