The US FDA approved Elacestrant for the treatment of postmenopausal women or adult men with advanced or metastatic breast cancer who are estrogen receptor positive, HER2 negative and have an ESR1 mutation who have experienced disease progression after receiving at least 1 line of endocrine therapy.
The FDA has also approved the Guardant360 CDx test as a companion diagnostic device to determine if patients can use Elacestrant.
Elacestrant is an oral selective estrogen receptor degrader (SERD) that received Fast Track designation from the FDA in 2018.
Estrogen receptor-positive, HER2-negative breast cancer is the most common type of breast cancer in the assortment, and ESR1 mutations predispose such patients to develop resistance to endocrine therapy, making this group of patients in urgent need of new treatment options.
Basis for approval.
Elacestrant was approved based on data from the randomised, open-label, active-controlled, multicentre Phase 3 EMERALD trial (NCT03778931).
The EMERALD trial enrolled a total of 478 patients with estrogen receptor-positive, HER2-negative breast cancer, approximately half of whom had ESR1 mutations. These patients had previously progressed in disease during 1 to 2 lines of endocrine therapy, with the 1st line of treatment containing CDK4/6 inhibitors. Some patients also had received 1st line chemotherapy in the setting of advanced or metastatic disease.
Enrolled patients were randomised 1:1 to two groups, one receiving 345 mg oral Elacestrant once daily and the other receiving endocrine therapy, including fulvestrant or an aromatase inhibitor, until disease progression or intolerable toxicity developed.
The results of the trial showed that patients treated with Elacestrant had a 45% reduced risk of disease progression or death compared to endocrine therapy. Among 228 (48%) patients with ESR1 mutations, the mean progression-free survival was 3.8 months in the Elacestrant group compared to 1.9 months in the endocrine therapy group. In patients without ESR1 mutations, there was no significant difference in progression-free survival between the two groups.
In terms of safety, assorted adverse reactions observed in at least 10% of patients treated with Elacestrant included musculoskeletal pain, nausea, elevated cholesterol, elevated aspartate aminotransferase, elevated triglycerides, fatigue, decreased haemoglobin, vomiting, elevated alanine aminotransferase, decreased sodium, increased creatinine, decreased appetite, diarrhoea, headache, constipation, abdominal pain, hot flushes and poor digestion.
The investigators said, "The results of this trial confirm the benefits of Elacestrant and suggest that in the future Elacestrant is expected to be a preferred treatment for patients with estrogen receptor-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer, which would greatly benefit such patients."
