By Maryam Lustberg, MD, MPH, as told to Keri Wiginton
Lustberg is director of the Center for Breast Cancer at Smilow Cancer Hospital and Yale Cancer Center, chief of breast medical oncology at Yale Cancer Center, and professor of medicine (medical oncology) at Yale School of Medicine. The information here reflects her clinical knowledge and experience. She was not involved in the development of elacestrant (Orserdu).
Hormone receptor-positive, HER2-negative breast cancer grows in response to signals from hormones such as estrogen. Endocrine therapies can block those signals, sometimes for months or years. But advanced or metastatic breast cancer may eventually change in a way that helps it resist treatment.
One such change is an ESR1 mutation. This alteration affects the estrogen receptor and can allow cancer cells to keep receiving growth signals even when earlier hormone therapies no longer work as well.
Elacestrant (Orserdu) is a type of endocrine therapy called a selective estrogen receptor degrader, or SERD.
Here’s what to know about who the drug may benefit, how well it works, and what taking it may be like.
Who is elacestrant for?
Elacestrant is for postmenopausal women and adult men with estrogen receptor-positive, HER2-negative advanced or metastatic breast cancer. Your cancer also needs to have an ESR1 mutation and to have progressed after at least one line of endocrine therapy.
That’s a very specific group. This isn’t a drug for every type of breast cancer, and an ESR1 test is an important part of deciding whether it’s right for you.
What is an ESR1 mutation, and how do doctors find it?
ESR1 is a gene that tells cells how to make the estrogen receptor.
After long-term endocrine therapy, especially aromatase inhibitors, some hormone receptor-positive breast cancers develop changes in the ESR1 gene. These changes can keep the receptor active even when estrogen levels are very low, allowing cancer cells to continue getting growth signals.
Your doctor can look for ESR1 mutations and other tumor-related changes with a type of blood sample called a liquid biopsy or on newly collected tumor tissue. These tests look for tumor DNA and help show what may be driving your cancer now and whether elacestrant may be a good choice for you.
How is elacestrant different from other hormone treatments?
Aromatase inhibitors lower the amount of estrogen your body makes. Elacestrant and other SERDs work differently by targeting the estrogen receptor itself and helping break it down.
Think of estrogen as a message and the receptor as the place where that message lands. Aromatase inhibitors reduce the number of messages, while SERDs reduce the number of places they can land. This makes it harder for cancer cells to receive signals that help them grow.
An important thing to highlight is that this is an oral therapy you can take in the comfort of your own home, which means less time in an infusion suite hooked up to an IV.
Why isn’t it the first hormone treatment you get?
ESR1 mutations often develop after cancer has been exposed to endocrine therapy. The mutation may not be present when treatment first begins.
Elacestrant was studied in people whose advanced or metastatic breast cancer had already started growing on earlier endocrine therapy. That’s another reason why doctors generally consider it after treatment resistance happens.
How well does elacestrant work?
The phase 3 EMERALD trial included 478 people with estrogen receptor-positive, HER2-negative advanced or metastatic breast cancer. Everyone’s cancer had progressed after earlier endocrine therapy that included a CDK4/6 inhibitor.
The results that led to FDA approval focused on 228 people whose tumors had an ESR1 mutation. This included postmenopausal women or men who’d received either elacestrant or another endocrine therapy chosen by their doctor, such as fulvestrant or an aromatase inhibitor.
The median progression-free survival in the ESR1-mutation group was:
- 3.8 months with elacestrant
- 1.9 months with standard endocrine therapy
Progression-free survival is the amount of time the cancer stays under control before it grows or spreads. A median is the midpoint, which means some people had shorter responses and others had longer ones.
A closer look at people whose cancer had stayed under control for at least 12 months with earlier endocrine therapy plus a CDK4/6 inhibitor found a larger benefit with elacestrant.
In this group, the median progression-free survival was:
- 8.6 months with elacestrant
- 1.9 months with standard endocrine therapy
These results suggest that elacestrant may work especially well when the cancer has already shown that it remains sensitive to endocrine therapy. These numbers are averages, so some people may have a much longer response.
How fast does it work?
Elacestrant needs some time to show its full effect. During the first month or two, your health care team will look at how you feel, whether your symptoms improve or stay stable, and what your blood tests show, including liver and kidney function.
You’ll usually have a follow-up scan within two or three months. If elacestrant is working, the scan may show that the tumors have shrunk or stayed the same size. Your symptoms, lab results, and scans all help your oncologist judge how well the treatment is controlling the cancer.
What side effects does elacestrant cause?
Most people tolerate elacestrant well. The most common side effects are:
Elacestrant can also raise cholesterol and triglycerides or cause changes in blood counts and liver, kidney, or electrolyte test results. Your care team will check bloodwork, including your lipid levels, before and during treatment.
Tell your care team about any side effects that bother you. Your doctor may pause the drug, lower the dose, or help treat a specific symptom so you can stay on treatment safely. For example, taking the pill with food may help lessen nausea or vomiting.
How do you take it?
You take one tablet once a day with food, ideally around the same time each day. You swallow it whole without crushing, splitting, or chewing it.
If your dose is more than six hours late, skip it and take your next dose at the usual time the following day. Follow the same advice if you throw up after taking it.
You can stay on it for as long as it controls the cancer and you can tolerate the side effects.
How often will you need follow-up care?
Because elacestrant is an oral treatment, you don’t need to spend time in an infusion center to get it. We usually see people more often when they first switch treatments, often about once a month.
If you’re doing well, you may eventually be able to spread visits further apart. You’ll still need regular blood tests and scans every few months so your oncologist can check whether the drug is working and watch for side effects.
Tell your care team about symptoms that come up between visits. You don’t need to wait until your next appointment to bring up a side effect.
Who shouldn’t take it?
Elacestrant works gradually, like other endocrine therapies. Your oncologist may suggest a faster-acting treatment if the cancer is growing quickly, making you very sick, or affecting how well a major organ works.
Cancer that has spread to the liver may still be treated with elacestrant. What matters most is how quickly the cancer is changing and whether your liver is still working well. People with severe problems may need another treatment.
Tell your health care team about every medicine, vitamin, and supplement you take. Some drugs affect an enzyme called CYP3A4 and can change the amount of elacestrant in your body.
Elacestrant can harm a fetus. People who could become pregnant, and men with partners who could become pregnant, should use birth control during treatment and for one week after the last dose. Avoid breastfeeding while taking it and for one week afterward.
Does insurance cover it? Is there a generic?
Coverage depends on your insurance plan. Even when elacestrant is covered, you may still have large medical bills if you have a high copay or deductible.
Tell your cancer center if cost is a concern. Financial counselors or specialty pharmacy teams can appeal a denial, check patient assistance programs, and look for other ways to lessen your out-of-pocket costs.
Elacestrant is a new drug, so there isn’t a generic version yet.
How can you find out if elacestrant is right for you?
Start by learning the basic details of your breast cancer and what may be driving it now.
You can ask your oncologist:
- Is my cancer HR-positive and HER2-negative?
- Has my cancer had genomic testing?
- Should I have a liquid biopsy?
- Does my cancer have an ESR1 mutation?
- What treatment options do I have at this point?
- How do you choose one treatment over another?
You don’t need to become an expert in breast cancer. But understanding your subtype and test results can help you take part in treatment decisions and ask more informed questions.
What are you excited about in the field of SERDs?
Oral SERDs give doctors a newer way to target estrogen-driven breast cancer. Researchers are now studying elacestrant with other targeted drugs and looking at whether using SERDs earlier could help delay or overcome treatment resistance.
Right now, elacestrant is approved for ESR1-mutated, estrogen receptor-positive, HER2-negative advanced or metastatic breast cancer that has progressed after at least one endocrine therapy.
As research continues, SERDs may play a larger role in breast cancer care. For now, treatment decisions depend on your cancer’s biology, how quickly it’s changing, your treatment history, and what matters most to you.
