What to do after breast cancer develops resistance to endocrine therapy? Elacestrant significantly improves progression-free survival.
Estrogen receptor 1 (ESR1) mutations are an important driver of resistance to endocrine therapy in patients with advanced/metastatic ER-positive/HER2-negative breast cancer. Treatment options for these patients are very limited after drug resistance. RECENTLY, THE RESULTS OF THE TWO MAIN ENDPOINTS OF THE EMERALD TRIAL SHOWED THAT compared with STANDARD ENDOCRINE THERAPY, Elacestrant has clinically SIGNIFICANT IMPROVEMENTS IN THE PROGRESSION-free SURVIVAL (PFS) OF PATIENTS PREVIOUSLY TREATED WITH ENDOCRINE THERAPY AND CDK 4/6 INHIBITORS.
Elacestrant International Research Data
EMERALD is an international multicenter, OPEN-label, ACTIVE-CONTROLLED TRIAL (NCT03778931). THE RESEARCHERS compared the SAFETY and EFFECTIVENESS of Elacestrant with SOC OPTIONS (SUCH as fluvestrant OR aromatase INHIBITORS). It is suitable for all ER-positive and HER2-negative POSTMENOPAUSAL WOMEN and MEN.Patients with sexual breast cancer, regardless of the ESR1 mutation status, especially those with any ESR1 mutations determined by circulating tumor DNA.
To meet the conditions for admission, patients need to be at least 18 years old or above and have progressed or relapsed after receiving first- or second-line endocrine therapy. Among them, first-line endocrine therapy must be the use of CDK4/6 inhibitors to treat ER-positive and HER2-negative metastatic breast cancer. They also need to have received at least one chemotherapy regimen in advanced/metastatic disease, have a measurable disease according to THE RECIST v1.1 standard, and have an ECOG performance of 0 or 1.
A total of 466 patients were recruited for the trial plan. Study participants randomly received Elacestrant in a 1:1 ratio at a daily dose of 400 mg, or fluvestrant or aromatase inhibitors selected by the researcher. The patients were stratified according to the ESR1 mutation status (yes or no), the previous fluvestrone (yes or no), and whether there is visceral metastasis (yes or no).
The primary endpoint of the trial was progression-free survival (PFS) assessed by an independent review committee (IRC) in all patients and the subgroup with ESR1 mutations. A key secondary endpoint was overall survival in both groups. Other endpoints, regardless of subgroup, included IRC-assessed objective response rate (ORR); duration of response (DOR); clinical benefit rate (CBR); investigator-assessed PFS, ORR, DOR, and CBR; safety and tolerability; pharmacokinetics; and patient-reported outcomes. Other exploratory endpoints included duration of chemotherapy, alterations in ctDNA associated with ER-positive disease and the CDK4/6 pathway and their correlation with response, and tumor-specific gene, protein, and RNA alterations associated with oncogenic pathways and proliferation in tissue biopsies. Data from this trial are expected to be presented at the 2021 San Antonio Breast Cancer Symposium.
Furthermore, a phase 1 trial (NCT02338349) evaluated 400 mg doses in 40 patients with ER-positive, HER2-negative advanced breast cancer, demonstrating good tolerability and monotherapy activity, even in patients with ESR1 mutations. Specifically, SERD induced an overall response rate (ORR) of 19% and a progression-free survival (PFS) of 4.5 months in this population. In a subgroup of patients with ESR1 mutations, the ORR was 33%. Patients who had previously received CDK4/6 inhibitors and fulvestrant also responded to treatment.
Elacestrant drug introduction
Drug name: Elacestrant
Other names: RAD1901
Manufacturer: Menarini Group, Radius Health
Elacestrant is a selective estrogen receptor degrader (SERD), which is taken orally once a day. Previous studies have shown that it can be used as a monotherapy or in combination with other treatments to treat breast cancer patients. Elacestrant is the first oral SERD to show positive top-line results in the treatment of ER-positive, HER2-negative advanced or metastatic breast cancer as a monotherapy with SOC in a key trial.
In preclinical models of ER-positive breast cancer and several xenograft models from severe patients, Elacestrant has been shown to have antitumor activity. SERD has also been found to be active in models resistant to CDK4/6 inhibitors and fluvestrone (Faslodex), including those carrying ESR1 mutations.
Reminder: Advanced/metastatic ER-positive and HER2-negative BREAST CANCER pretreated BY ENDOCRINE THERAPY IS STILL A HIGHLY UNMET MEDICAL NEED AREA. EMERALD'S TRIAL RESULTS PROVIDE significant PROGRESS FOR PATIENTS SUFFERING FROM THIS DEVASTATING DISEASE. Progress. It is hoped that Elacestrant will be approved as soon as possible and used in clinical practice as soon as possible for the benefit of more cancer patients.
