Experimental Elacestrant Shows Promise for Pre-Treated Metastatic, Hormone Receptor-Positive, HER2-Negative Breast Cancer
The experimental hormonal therapy elacestrant offered better progression-free survival than standard hormonal therapy for post-menopausal women and men diagnosed with metastatic, hormone receptor-positive, HER2-negative breast cancer that had grown during treatment with hormonal therapy and a CDK4/6 inhibitor, according to the EMERALD study.
Progression-free survival is how long people live without the cancer growing.
The research was presented on Dec. 8, 2021, at the San Antonio Breast Cancer Symposium. Read the abstract of “Elacestrant, an oral selective estrogen receptor degrader (SERD), vs investigator’s choice of endocrine monotherapy for ER+/HER2- advanced/metastatic breast cancer (mBC) following progression on prior endocrine and CDK4/6 inhibitor therapy: Results of EMERALD phase 3 trial.”
Aditya Bardia, MD, MPH, director of the breast cancer research program at Mass General Cancer Center, recently joined the Breastcancer.org Podcast to discuss the EMERALD study.
Like Faslodex (chemical name: fulvestrant), elacestrant is a type of hormonal therapy called a selective estrogen receptor downregulator or degrader (SERD). SERDs work by blocking the effects of estrogen on hormone receptor-positive breast cancer cells by sitting in the estrogen receptors on the cells. If a SERD is in the receptor, there is no room for estrogen to attach itself to the cell. If estrogen isn’t attached to the cancer cell, the cell doesn’t receive estrogen’s signals to grow and multiply.
reduce the number of estrogen receptors
change the shape of estrogen receptors so they don’t work as well
Faslodex is a liquid that is given once a month as an injection into a muscle, usually at a doctor’s office.
Elacestrant is a pill taken by mouth.
Many people would rather take a pill at home than go to a doctor’s office to get an injection, according to the researchers.
Elacestrant is not yet approved by the U.S. Food and Drug Administration (FDA) to treat breast cancer. But Radius Health — the company that makes elacestrant — plans to apply for FDA approval in 2022.
About CDK4/6 inhibitors
CDK4/6 inhibitors are a class of medicines used to treat certain types of hormone receptor-positive, HER2-negative breast cancers. These medicines target specific proteins known as cyclin-dependent kinases 4 and 6, abbreviated as CDK4/6. These kinases help control cell division. CDK4/6 inhibitors work by interfering with the kinases and stopping cancer cells from dividing and growing.
Currently, there are three CDK4/6 inhibitors used to treat breast cancer:
Ibrance (chemical name: palbociclib)
Kisqali (chemical name: ribociclib)
Verzenio (chemical name: abemaciclib)
About the EMERALD study
The EMERALD study included 477 post-menopausal women and men diagnosed with metastatic, hormone receptor-positive, HER2-negative breast cancer that had grown while being treated with hormonal therapy and a CDK4/6 inhibitor.
Everyone in the study had received one or two previous hormonal therapy regimens, and no one had received chemotherapy for metastatic breast cancer.
The researchers randomly assigned the people to one of two treatments:
239 people received elacestrant
238 people received the standard of care, which was the researchers’ choice of either Faslodex or an aromatase inhibitor
After 12 months of follow-up, the researchers found that more people who received elacestrant were alive without the cancer growing than people who received the standard of care.
Progression-free survival rates were:
22.32% for people who took elacestrant
9.42% for people who received the standard of care
The researchers also looked at how well elacestrant worked against breast cancer with an ESR1 mutation. The ESR1 gene makes the estrogen receptor protein. When breast cancers develop an ESR1 mutation, the mutation changes the estrogen receptor and can make the cancer resistant to hormonal therapy.
Among people diagnosed with breast cancer that had an ESR1 mutation, progression-free survival rates were:
26.76% for people who took elacestrant
8.19% for people who received the standard of care
An early analysis suggested that people who took elacestrant had better overall survival than people who received the standard of care, but those results were not yet mature.
Elacestrant side effects
Like almost all cancer medicines, elacestrant can cause side effects, some of them severe.
Nausea was the most common side effect of elacestrant, experienced by 35% of people who took elacestrant versus 18.8% of people who received the standard of care. Still, only 2.5% of people taking elacestrant experienced more severe nausea.
Additional elacestrant side effects included:
fatigue, experienced by 19%
vomiting, experienced by 19%
joint pain, experienced by 14.3%
loss of appetite, experienced by 14.8%
diarrhea, experienced by 13.9%
back pain, experienced by 13.9%
Of all the people who stopped taking the medicine because of side effects:
6.3% were in the elacestrant group
4.4% were receiving the standard of care
“Elacestrant is the first oral SERD to demonstrate a statistically significant and clinically meaningful improvement of progression-free survival in patients with [estrogen receptor]-positive, HER2-negative metastatic breast cancer in the second- and third-line settings, including for patients whose tumors harbor ESR1 mutations,” said Dr. Bardia, who is also an associate professor at Harvard Medical School. “Elacestrant was well tolerated with manageable and reversible side effects. This therapy has the potential to become the new standard of care for patients with this cancer.”
What this means for you
If you’ve been diagnosed with metastatic, hormone receptor-positive, HER2-negative breast cancer that has grown during treatment with hormonal therapy and a CDK4/6 inhibitor, this study offers promising news.
“There are a number of oral SERDs in development by other companies,” Dr. Bardia told Breastcancer.org. “So this is great news for the field in general, that these oral SERDs could potentially be better than currently available endocrine therapy agents.”
Although the FDA hasn’t yet approved elacestrant to treat breast cancer in the United States, the medicine has received fast-track designation and may be approved in the next year.
In the meantime, you can talk to your doctor about whether a clinical trial on elacestrant makes sense for you and your unique situation.
Stayed tuned to Breastcancer.org’s Research News for the latest updates on elacestrant, including studies looking at elacestrant in combination with a CDK4/6 inhibitor.
Written by: Jamie DePolo, senior editor
— Last updated on July 30, 2022, 2:59 PM