|The following article features coverage from the 2021 San Antonio Breast Cancer Symposium. Click here to read more of Cancer Therapy Advisor’s conference coverage.|
Elacestrant is the first oral selective estrogen receptor degrader (SERD) that demonstrated significant and clinically meaningful improvement in progression-free survival compared with standard of care endocrine therapy in men and postmenopausal women with estrogen receptor-positive (ER+)/ HER2-negative (HER2-) metastatic breast cancer in the second/third line after treatment with a CDK4/6 inhibitor.
“Clinically, elacestrant has the potential to become the new standard of care in the studied patient population,” said Aditya Bardia, MD, MPH, director of the breast cancer research program at Mass General Cancer Center in Boston, and associate professor at Harvard Medical School, who presented results from the EMERALD trial at the 2021 San Antonio Breast Cancer Symposium (SABCS).
According to Dr Bardia, endocrine therapy plus a CDK4/6 inhibitor is the mainstay for the management of ER+/HER2- metastatic breast cancer as first-line therapy. However, most patients will eventually experience disease progression, including development of ESR1 mutations.
In the post-CDK4/6 setting, standard single-agent endocrine therapy is associated with a median progression-free survival of about 2 months, highlighting the clinical need for better endocrine therapy for these patients, Dr Bardia said.
Elacestrant is an oral SERD that blocks ER in a dose-dependent manner and has demonstrated clinical activity in a phase 1 clinical trial for postmenopausal women with ER+/HER2- metastatic breast cancer.
In EMERALD (ClinicalTrials.gov Identifier: NCT03778931), 477 patients were randomly assigned to receive elacestrant or investigator’s choice standard of care endocrine therapy. The researchers had coprimary endpoints of progression-free survival in all patients and in those patients with mutant ESR1.
Elacestrant showed a statistically significant and clinically meaningful progression-free survival improvement compared with standard of care. In all patients, elacestrant was associated with a 30% reduction in the risk of progression or death (hazard ratio [HR], 0.697; 95% CI, 0.552-0.880). Median progression-free survival was 2.79 months with elacestrant compared with 1.91 months with standard of care (P =.0018).
In patients with mutant ESR1, elacestrant was associated with a 45% reduction in the risk of progression or death (HR, 0.546; 95% CI, 0.387-0.768). Median progression-free survival was 3.78 months for elacestrant compared with 1.87 months for standard of care (P =.0005).
Progression-free survival at 12 months in both all patients and patients with mutant ESR1 that received elacestrant was higher compared with standard of care endocrine therapy. Progression-free survival at 12 months with elacestrant was 22.3% in all patients compared with 9.4% for standard of care. In patients with mutant ESR1, the 12-month progression-free survival rate was 26.8% in patients who received elacestrant compared with 8.2% in patients who received standard of care.
Multiple prespecified subgroups showed a consistent trend for elacestrant compared with standard of care, including patients that had received prior fulvestrant.
Dr Bardia also presented interim overall survival results. There was a trend toward improved overall survival in patients that received elacestrant compared with standard of care. Final overall survival results are expected in late 2022/early 2023, Dr Bardia said.
Elacestrant was well tolerated with a predictable and manageable safety profile consistent with other endocrine therapies. Treatment-emergent adverse events leading to discontinuation of elacestrant or standard of care were infrequent in both arms (6.3% vs. 4.4%). There were no treatment-related deaths in either group.
Disclosures: This research was supported by Radius Health. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Read more of Cancer Therapy Advisor’s coverage of SABCS 2021 by visiting the conference page.
Bardia A, Neven P, Streich G, et al. Elacestrant, an oral selective estrogen receptor degrader (SERD), vs investigator’s choice of endocrine monotherapy for ER+/HER2- advanced/metastatic breast cancer (mBC) following progression on prior endocrine and CDK4/6 inhibitor therapy: results of the EMERALD phase 3 trial. Presented at SABCS 2021; December 7-10, 2021; San Antonio, TX. Abstract GS2-02.