Elacestrant has the potential to become the "new standard of care" in this patient population, Dr. Aditya Bardia of Massachusetts General Hospital Cancer Center, Harvard Medical School, in Boston, said in presenting the results during a press briefing at the San Antonio Breast Cancer Symposium.
"Elacestrant is off to a great start in the race to replace fulvestrant with oral SERDs, of which several are in development," Dr. Charles Shapiro, professor of medicine, hematology and medical oncology at Icahn School of Medicine at Mount Sinai in New York, who wasn't involved in the study, told Reuters Health by email.
Endocrine therapy plus a CDK4/6 inhibitor is the mainstay of first-line management of ER+/HER2- metastatic breast cancer (mBC). However, most patients with ER+ metastatic breast cancer eventually experience disease progression, including development of ESR1 mutations.
In the post-CDK4/6-inhibitor setting, standard single-agent endocrine therapy such as fulvestrant, which is given via intramuscular injection, is associated with a median progression-free survival (PFS) of around two months, "highlighting the critical need for better endocrine therapy" for these patients, Dr. Bardia explained.
Elacestrant is an oral SERD that blocks ER in a dose-dependent manner that has previously shown clinical activity in postmenopausal women with ER+/HER2- mBC.
The EMERALD study enrolled 477 postmenopausal women with ER+/HER2- mBC who had received one or two prior lines of endocrine therapy without chemotherapy in the metastatic setting, and who had progressed on prior treatment with a CDK4/6 inhibitor. They were randomly allocated to elacestrant or standard of care (fulvestrant or an aromatase inhibitor).
Treatment with elacestrant was associated with a 30% reduction in the risk of disease progression or death compared with standard-of-care. Among women whose tumors had ESR1 mutations, elacestrant was associated with a 45% reduced risk of death or disease progression, Dr. Bardia reported.
At 12 months, the rate of PFS was significantly higher with elacestrant than with standard-of-care (22.3% vs. 9.4%). PFS rates at 12 months among those with ESR1-mutated tumors were 26.8% and 8.2%, respectively, he noted.
An interim analysis of overall survival showed a trend in favor of elacestrant, including in patients with ESR1-mutated tumors, with a final overall survival analysis expected next year, Dr. Bardia said.
Elacestrant was well tolerated with a "predictable and manageable" safety profile consistent with other endocrine therapies.
"Elacestrant is the first oral SERD that has demonstrated a statistically significant and clinically meaningful improvement in PFS versus standard-of-care endocrine therapy in a randomized global phase-3 study" of ER+/HER2- mBC in second- and third-line, post-CDK4/6 inhibitor setting, Dr. Bardia told the briefing.
Briefing co-moderator Dr. Carlos Arteaga, director of the Simmons Comprehensive Cancer Center at UT Southwestern Medical Center, in Dallas, said, "The results clearly suggest that this new SERD may be a new treatment option for patients with breast cancer, not only as a single therapy, but also in combination with other targeted therapies."
Dr. Shapiro told Reuters Health, "The subsequent trial for elacestrant is likely to be in front or second endocrine therapy and combined with CDK 4/6 inhibitors. In this setting, clinically meaningful benefits are likely to be established for this drug."
The study was supported by Radius Health, which is developing elacestrant. Dr. Bardia has financial ties to the company.
SOURCE: https://www.sabcs.org/ San Antonio Breast Cancer Symposium (SABCS), held December 7-10, 2021.
By Megan Brooks
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