Orserdu (elacestrant) is a targeted hormonal therapy for breast cancer. Unlike chemotherapy, which can harm both healthy and cancer cells, targeted therapy aims at specific proteins in the cancer cells that drive them to grow more quickly than normal. The FDA approved Orserdu in 2023 for certain types of advanced breast cancer that are positive for estrogen receptor (ER-positive) and negative for human epidermal growth factor receptor 2 (HER2-negative), and have changes in a gene called ESR1. It is approved for women after menopause or adult men whose cancer has worsened after they took other types of hormonal cancer medicines. Orserdu is a pill taken once a day.
How Does Orserdu Work in Breast Cancer?
ER-positive breast cancer cells rely on the hormone estrogen in the blood to grow. Some hormonal cancer medicines stop the cancer by blocking estrogen from reaching these cells.
Some people with ER-positive, HER2-negative breast cancer develop changes in a gene called ESR1 after taking these medicines, which can make them less effective. As a result, the cancer may get worse. Orserdu works by binding to estrogen receptors on cancer cells, so there is no room for estrogen to attach to these receptors, in people who have changes in the ESR1 gene and do not respond to previous hormonal therapies.
Is Orserdu Right for Me?
Orserdu may be the right choice for you if:
- You are a woman after menopause or an adult man with ER-positive, HER2-negative breast cancer.
- Your cancer is advanced or has spread to other parts of your body (metastatic).
- You have ESR1 gene changes confirmed by specific tests.
- Your cancer has grown while or after you took at least one other cancer hormonal medicine.
Your doctor will test your cancer for gene changes and review your medical history to decide if Orserdu is right for you.
How Was Orserdu Studied for Treating ER-Positive, HER2-Negative Breast Cancer?
One clinical study, the EMERALD trail, was done to look at the benefits and risks of Orserdu in people with ER-positive, HER2-negative advanced or metastatic breast cancer and ESR1 gene changes.
The main question this study wanted to answer was:
How well does Orserdu work, compared with other hormonal cancer medicines, for people with ER-positive, HER2-negative breast cancer and ESR1 gene changes, whose cancer got worse after at least one other hormonal medicine?
To learn this, the researchers measured how long it took for the people who took Orserdu to have their cancer get worse, compared to those who took other medicines. This is called “progression-free survival” and shows how well a medicine controls a disease.
What medicines did the people in the study take?
About half of the people in the study were randomly selected to take Orserdu, and the other half took other hormonal cancer medicines including anastrozole, exemestane, fulvestrant, or letrozole.
Who was included in the study?
To take part in the study, people had to:
- Be a woman after menopause or a man at least 18 years old (adult)
- Have advanced or metastatic ER-positive and HER2-negative breast cancer that could not be cured with surgery or radiation therapy
- Have taken one or two types of hormonal cancer medicines combined with a group of medicines called CDK4/6 inhibitors, which stop the breast cancer cells from multiplying
- Have gotten a maximum of one type of chemotherapy for advanced or metastatic cancer
- Have changes in the ESR1 gene, confirmed by specific tests
Who was excluded from the study?
People could not be in this study if they:
- Had previously taken cancer medicines that work in a similar way to Orserdu
- Had hormonal therapy or chemotherapy within a few weeks before the study
- Had widespread cancer that caused severe problems in the body’s essential organs, like the lungs and liver (visceral disease)
What was the study population?
- A total of 477 people were in this study. A total of 239 of them took Orserdu and 238 took other cancer hormonal medicines.
- About 98% were women and about 2% were men.
- About 48% of the people in the study had changes in their ESR1 gene.
- Among the people with ESR1 gene changes:
- All were women.
- The age ranged from 28 to 89 years.
- About 72% were White, 6% were Asian, 4% were Black, 9% were Hispanic/Latino, and 19% were from other racial backgrounds.
- About 62% had taken one type and 39% had taken two types of cancer hormonal medicine for advanced or metastatic cancer.
- All had gotten medicines from the CDK4/6 inhibitor group, 24% had taken fulvestrant, and 25% had gotten chemotherapy for advanced or metastatic cancer.
How long was the study?
People continued taking Orserdu or other hormonal cancer medicines, as assigned, until their cancer got worse, they had unacceptable side effects, or either they or the study doctors decided that they should stop being in the study.
The people in the study were followed for about 2 years.
What Were the Main Benefits of Orserdu Seen in the Study?
Progression-free survival
People who took Orserdu lived significantly longer before their cancer worsened, compared to those who took other hormonal cancer medicines.
- After 6 months, about 34% of all the people taking Orserdu did not see their cancer get worse, compared to about 20% of people taking other hormonal cancer medicines. For those with ESR1 gene changes, about 41% of people taking Orserdu did not see their cancer get worse, compared to about 19% of those on other hormonal cancer medicines.
- After 12 months, about 22% of all people taking Orserdu did not see their cancer get worse, compared to about 9% on other hormonal cancer medicines. For those with ESR1 gene changes, about 27% of people taking Orserdu did not see their cancer get worse, compared to about 8% on other hormonal cancer medicines.
What Are the Possible Side Effects of Orserdu, and How Can I Prevent or Manage Them?
Common side effects of Orserdu include muscle and joint pain, headaches, nausea, hot flushes, reduced appetite (when you don’t feel like eating as usual), tiredness, vomiting, diarrhea, constipation, or an upset stomach. These side effects are usually mild and go away on their own.
To help with nausea, vomiting, diarrhea, constipation, or an upset stomach, try:
- Adding fruits and vegetables to your diet
- Dividing your daily meals in multiple smaller portions
- Staying away from greasy or heavy meals
To help with a reduced appetite, try:
- Eating when you feel like it throughout the day
- Drinking shakes or liquid meal replacements
- Adding dried herbs or other mild spices to your meals
To help with hot flushes, try:
- Wearing light and loose-fitting clothes
- Bringing down your stress levels; for example, by practicing slow-breathing techniques
To help with muscle and joint pain or a headache, your pharmacist may suggest taking non-prescription pain medicines like acetaminophen or ibuprofen.
Orserdu may also affect the fat (cholesterol and triglyceride) levels in your blood, how your liver or kidneys work, blood cell counts, or the salt levels in your blood. Your doctor will regularly check your blood, liver, and kidneys.
Be sure to let your doctor know if the side effects don’t go away or get worse.
Serious side effects that Orserdu can cause include high fat (cholesterol and triglyceride) levels in your blood. Your doctor will check your cholesterol and triglyceride levels before you start and while you are taking Orserdu.
These are not all the possible side effects of Orserdu. Contact your health care provider for medical advice about side effects if you are having symptoms that bother you. You can report side effects to the FDA at 800-FDA-1088 (800-332-1088).
How Do I Know if Orserdu Is Working?
Your health care provider will regularly check how well Orserdu is working for your cancer by looking at results of tests such as blood tests and CT scans, MRI scans, and bone scans. Take Orserdu exactly as your health care provider tells you. Do not change your dose or stop taking Orserdu unless your health care provider tells you.
How Do Other Medicines or Foods Interact With Orserdu?
Tell your pharmacist and other health care providers about all the other prescription and non-prescription medicines, vitamins, supplements, and herbal products you take before starting Orserdu. Some medicines and foods may interfere with how Orserdu works in your body. Similarly, Orserdu can affect other medicines.
This is because some foods and medicines can interfere with one of the proteins that help break down Orserdu before it leaves your body, called CYP3A.
Foods or medicines that can stop CYP3A from working are called CYP3A inhibitors, while those that can make it more active are called CYP3A inducers.
CYP3A inhibitors make Orserdu linger in your body longer than it should, causing more side effects. Medicines in this group include but are not limited to:
- Some antibiotics, like ciprofloxacin and erythromycin
- Some antifungals, like fluconazole, itraconazole, and ketoconazole
- Some HIV medicines, like boceprevir and telaprevir
- Some medicines that slow down the immune system, like cyclosporine
- Some heart and blood pressure medications, like diltiazem and verapamil
- Some mood support medicines (antidepressants), like fluvoxamine
- Some fruits, like grapefruits, pomelos, Seville oranges, and star fruit
CYP3A inducers cause Orserdu to leave your body quicker, making it less effective. Medicines in this group include but are not limited to:
- Some seizure medicines, like carbamazepine, phenobarbital, phenytoin, and primidone
- Some antibiotics, like rifampin
- Some HIV medicines, like efavirenz
- Some natural medicines, like St. John’s wort
Orserdu, in turn, may increase the levels of some other medicines in the blood, causing side effects of those medicines. Medicines in this group include but are not limited to:
- Some heart medicines, like digoxin
- Some medicines that lower cholesterol, like rosuvastatin
These are not all the possible interactions with Orserdu. Talk to your health care provider before starting any other prescription and non-prescription medicines, vitamins, supplements, and herbal products while you are on Orserdu. They will decide if you need to stop taking a medicine or avoid certain foods while you are taking Orserdu, or if you need to adjust your dose of Orserdu or other medicines. Your pharmacist can tell you which foods or medicines interact with Orserdu.
How Can I Get Orserdu?
You will need a prescription from a cancer specialist (oncologist). Orserdu is only available at specialty pharmacies, and your doctor will arrange for you to get it.
If you need assistance paying for Orserdu, the drugmaker may be able to help you. Check out their Stemline ARC Patient Advocates program at https://www.Orserdu.com/savings-and-support/ to learn more about getting help with costs and your insurance coverage. You can also contact the drugmaker at 833-4-STEMLINE (833-478-3654).
