Elacestrant—an investigational oral selective estrogen receptor degrader (SERD)—achieved longer progression-free survival vs standard-of-care endocrine monotherapy as second- or third-line therapy in patients with estrogen receptor (ER)-positive, HER2-negative, advanced or metastatic breast cancer in the phase III EMERALD study. Additional analyses from EMERALD showed a median progression-free survival of up to 8.6 months dependent on the duration of prior treatment with CDK4/6 inhibitors (used as a surrogate for estrogen sensitivity). Safety was manageable and consistent with previous reports. These findings were presented by senior author Virginia Kaklamani, MD, and colleagues at the 2022 San Antonio Breast Cancer Symposium (Abstract GS3-01).
“These results show that when used as a single agent, elacestrant provided median progression-free survival of up to 8.6 months, based on the duration of previous CDK4/6 inhibitor therapy, with a manageable safety profile and the convenience of an oral tablet. This suggests elacestrant may have the potential to become a new standard of care as a monotherapy endocrine sequencing option in ER-positive, HER2-negative, advanced breast cancer after progression on CDK4/6 inhibitors, before moving to combination therapies,” said Dr. Kaklamani, a breast medical oncologist and Professor of Medicine at UT Health San Antonio MD Anderson Cancer Center. Dr. Kaklamani presented an in-depth analysis of progression-free survival according to the duration of prior CDK4/6 therapy and the presence of ESR1 mutations at the Symposium.
...Elacestrant may have the potential to become a new standard of care as a monotherapy endocrine sequencing option in ER-positive, HER2-negative advanced breast cancer after progression on CDK4/6 inhibitors, before moving to combination therapies.— Virginia Kaklamani, MD
Tweet this quote
EMERALD Trial
EMERALD is a phase III registrational trial that demonstrated statistically significant progression-free survival with elacestrant vs treatment with standard-of-care endocrine monotherapy (fulvestrant, letrozole, anastrozole, exemestane). The study met the co-primary endpoints in all patients (n = 239 in each arm) and in those patients harboring ESR1 mutations (115 in the elacestrant arm and 113 in the standard-of-care arm). EMERALD is unique among pivotal trials in second- and third-line settings in metastatic breast cancer in that all enrolled patients had to have experienced disease progression on prior CDK4/6 inhibitors in the metastatic setting. Prior fulvestrant and prior chemotherapy were allowed.
A post hoc analysis of progression-free survival based on the duration of prior CDK4/6 inhibitor therapy demonstrated that monotherapy with elacestrant achieved clinically meaningful gains, both in the total patient population as well as in patients with ESR1 mutations. A longer duration of prior CDK4/6 inhibitors was positively associated with longer progression-free survival on elacestrant but not with standard of care.
In the group of patients with prior exposure to CDK4/6 inhibitors of 12 months or longer, in all patients in the trial, elacestrant achieved a median progression-free survival of 3.8 months vs 1.9 months with the standard of care, representing a 39% reduction in the risk for disease progression or death. In the ESR1-mutated population, median progression-free survival was 8.6 months vs 1.9 months, reflecting a 59% reduction in the risk for disease progression or death.
In patients exposed to CDK4/6 inhibitors for 18 months or longer, in all patients, median progression-free survival was 5.5 months with elacestrant vs 3.3 months with the standard of care, for a 30% reduction in the risk for disease progression or death. Among the ESR1-mutated population, median progression-free survival was 8.6 months with elacestrant vs 2.1 months on the standard of care—a 53% reduction in the risk for disease progression or death.
Updated safety data were consistent with previous reports. Most of the adverse events, including nausea, were grade 1 or 2, and the rates of discontinuation of therapy due to an adverse event were low (3.4% and 0.9%, respectively).
Disclosure: Dr. Kaklamani has served as a consultant to AstraZeneca and received honoraria from Daiichi Sankyo, Genentech, Genomic Health, Gilead Sciences, Novartis, Pfizer, and Puma Biotechnology. For full disclosures of the other study authors, visit www.sabcs.org.
