Fulvestrant is also the only SERD approved for patients with breast cancer, according to the researchers.
Results from the phase 3 EMERALD trial found that the investigational oral selective estrogen receptor degrader (SERD) elacestrant significantly decreased the risk of death or disease progression and increased progression-free survival (PFS) compared with standard-of-care endocrine therapy for postmenopausal patients with estrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancers, according to a presentation from the San Antonio Breast Cancer Symposium 2021.
It is typical for patients with metastatic ER-positive breast cancer to be treated with endocrine therapy, such as fulvestrant, but resistance to this type of treatment is common because of mutation of the ESR1 gene. Fulvestrant is also the only SERD approved for patients with breast cancer, according to the researchers.
“There is an urgent unmet need for alternative SERDs that are effective against ER-positive metastatic breast cancer, including those with ESR1 mutations,” said Aditya Bardia, MD, MPH, director of the breast cancer research program at Mass General Cancer Center, and associate professor at Harvard Medical School, in a press release.
Unlike fulvestrant, elacestrant is administered orally and has greater absorption, improved pharmacokinetics, and enhanced inhibition of ER, according to the study. There is also greater antitumor activity in elacestrant seen in mouse models of ER-positive breast cancer.
The EMERALD trial marks elacestrant as the first oral SERD to be studied in a randomized phase 3 clinical trial. The trial enrolled 477 postmenopausal patients with ER-positive/HER2-negative metastatic breast cancer who had received 1 or 2 prior lines of endocrine therapy without chemotherapy in the metastatic setting and who had progressed on prior treatment with a CDK4/6 inhibitor.
The patients were then randomly assigned to take either elacestrant or standard of care. Among the entire patient population evaluated, 228 had tumors with mutated ESR1.
The study authors found that patients in the elacestrant arm had a 30% lower risk of death or disease progression compared with those in the standard-of-care arm. Further, among the patients whose tumors had ESR1 mutations, those in the elacestrant arm had a 45% reduced risk of death or disease progression. The subgroup analyses highlighted how elascestrant improved outcomes regardless of the presence of visceral metastases, the number of prior lines of therapy, pretreatment with fulvestrant, or geographic region, according to the study.
Among patients with ESR1-mutated tumors, those in the elacestrant arm had a significantly higher rate of PFS (26.76%) than those who received the standard of care (8.19%) at 12 months.
Specific grade 1 or 2 treatment-related adverse events (TRAEs) were more common among patients treated with elacestrant compared with standard of care, including nausea, vomiting, and fatigue. Additionally, grade 3 or higher TRAEs were observed among 7.2% of patients in the elacestrant arm compared with 3.1% of patients in the standard-of-care arm, according to the study.
“Elacestrant is the first oral SERD to demonstrate a statistically significant and clinically meaningful improvement of progression-free survival in patients with ER-positive/HER2-negative metastatic breast cancer in the second-and third-line settings, including for patients whose tumors harbor ESR1 mutations,” Bardia said in the press release. “Elacestrant was well tolerated with manageable and reversible side effects. This therapy has the potential to become the new standard of care for patients with this cancer.”
There was a study limitation, in that all enrolled patients had received prior treatment with a CDK4/6 inhibitor, causing the efficacy of elacestrant in patients without prior CDK4/6 inhibitor treatment to be unknown.
Bardia noted that future studies will seek to understand the efficacy of elacestrant during earlier lines of treatment and in combination with other therapies. Further, a phase 2 trial will examine the impact of elacestrant in combination with abemaciclib specifically for patients with brain metastases.
Elacestrant may improve outcomes for patients whose metastatic breast cancers progressed on prior endocrine therapy [news release]. San Antonio Breast Cancer Symposium; December 7, 2021. Accessed December 7, 2021. https://aacr.ent.box.com/s/hzzlsqgym93w8wxgpwtjegi0d5hfu6j2