Good news for the therapy of ER-positive HER2-negative metastatic breast cancer from San Antonio Breast Cancer Symposium: the selective estrogen receptor degrader (SERD) elacestrant has been shown to improve progression-free survival and seems to have a trend towards overall survival improvement in interim analysis, whose mature data are expected for late 2022 / early 2023.
Results come from the EMERALD phase 3 clinical trial, which involved 477 men and postmenopausal women who had received at least one or two lines of endocrine therapy, including one in combination with a CDK4/6 inhibitor, for ER-positive, HER2-negative, metastatic breast cancer; participants were given oral elacestrant 400 mg/day or physician’s choice of another treatment considered standard of care such as fulvestrant, anastrozole, letrozole or exemestane. The primary endpoint was progression-free survival and the results are encouraging in both global polulation and patients with ESR1 mutations: with elacestrant the median rose to 2.8 months versus 1.9 and the 12-month rates were 22.3% for elacestrant versus 9.4% for standard care. Treatment with elacestrant also significantly prolonged progression-free survival in patients harboring ESR1 mutations, with a median of 3.8 months and 12-month PFS rates of 26.8% versus 8.2%. The overall survival trend was also favorable and the treatment showed a predictable and manageable safety and tolerability profile, consistent with other endocrine therapies: the most common adverse events were nausea and back pain and a total of 2.5% of patients required a dose reduction, while 3.4% discontinued treatment.
Presenting data Aditya Bardia of Massachusetts General Hospital in Boston stressed that in these patients combined endocrine plus CDK4/6 inhibitor therapy is “the mainstay” for the first-line treatment, but most patients develop resistance, some via acquired ESR1 mutations; good results obtained with elacestrant also in this subgroup of tumors suggest that SERD may be superior to standard endocrine therapy and could therefore become a new therapeutic option in this population. «Further elacestrant combinations in earlier lines and with other targeted therapies, including CDK4/6 and mTOR inhibitors, are ongoing/planned for patients with ER-positive, HER2-negative breast cancer», Bardia concluded.