What to Know About Oral SERDs: A Promising New Group of Medications for Breast Cancer
Key takeaways:
Oral selective estrogen receptor degraders (SERDs) are a developing group of medications for estrogen receptor-positive breast cancer.
The only SERD that’s FDA approved is an injection called fulvestrant (Faslodex). Many oral SERDs are being studied in clinical trials, but none of them are FDA approved yet.
Elacestrant is an oral SERD that’s pending FDA approval. It helped improve the time without seeing cancer growth in certain people with advanced breast cancer in clinical trials.
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It seems like every week we hear about a new medication for cancer. But why do we need so many? Well, our knowledge about cancer continues to expand. As a result, new and improved treatment options continue to come to market.
Breast cancer is no exception. Health experts already know that estrogen and its receptors (chemical binding sites) can lead to cancer growth for people with estrogen receptor-positive (ER-positive) breast cancer. Decreasing estrogen’s effects on breast cancer cells is a common treatment for this type of cancer. Selective estrogen receptor modulators (SERMs) and aromatase inhibitors (AIs) are commonly used for this purpose.
However, these medications don’t work for everybody. New and improved treatments are still needed for this form of cancer. This is where a group of medications called selective estrogen receptor degraders (SERDs) come into play.
One SERD, fulvestrant (Faslodex), is already available. But it only comes as an injection, and you need to visit your healthcare provider’s office to receive it. It also has dosing instructions that make it less than ideal, including multiple injections over time into your buttocks.
To help with this, researchers are working on developing oral SERDs. They’re aiming to make them more convenient and effective than injectable SERDs like fulvestrant. So far, no oral SERDs have been approved by the FDA, but there are a number in clinical trials that could be approved in the near future.
What are SERDs?
SERDs are medications that treat ER-positive breast cancer. There’s currently only one SERD that’s FDA approved for use — fulvestrant. After a few initial doses during the first month of treatment, it’s injected once a month over time. It can be given alone or in combination with other breast cancer treatments.
On top of fulvestrant, several oral SERDs are being studied in clinical trials. Early data suggests that they could be helpful new options for people with ER-positive breast cancer in the future. They’re mostly being studied for advanced stages of breast cancer.
How do SERDs work?
SERDs block estrogen’s access to estrogen receptors all throughout your body. They also destroy these receptors and help prevent your body from making more of them in the future.
This is especially helpful if you have ER-positive breast cancer that is resistant to treatment with medications that block or lower estrogen. Sometimes this is due to a mutation called ESR1. Blocking and destroying these receptors helps prevent cancer growth.
SERDs vs. SERMs — what’s the difference?
You’ve likely heard of a medication called tamoxifen. A type of SERM, it prevents and treats ER-positive breast cancer. Other SERMs include raloxifene (Evista) and toremifene (Fareston).
SERDs are different from SERMs. As mentioned, SERDs block estrogen receptors throughout your body. SERMs enhance estrogen activity in some parts of your body, but they block it in others.
SERMs block estrogen in breast tissue, which helps prevent breast cancer growth. But they enhance estrogen activity in other parts of your body, such as the lining of your uterus. This increases the risk of uterine cancer. They also have positive and negative effects on other parts of your body, such as your bones, platelets, and cardiovascular system. SERDs aren’t thought to have these effects.
What are the risks and side effects of oral SERDs for breast cancer?
So far, side effect information is available from a phase 3 trial for one oral SERD — elacestrant. It seems to have similar side effects to other breast cancer medications that affect estrogen receptors. These are known as endocrine therapies. The most common side effects in a recent elacestrant study included:
Nausea
Vomiting
Fatigue
Decreased appetite
Joint pain
Diarrhea
Back pain
Liver irritation
Headache
Constipation
Hot flushes
Compared to people who took an AI or fulvestrant, nausea was the only side effect that happened more in people who took elacestrant. However, this difference may or may not be clinically meaningful. We’ll learn more about oral SERD side effects as clinical trials roll on.
What oral SERDs are currently in development for breast cancer treatment?
Elacestrant is the only oral SERD that’s completed a phase 3 study. This is typically the last step to take before a drug manufacturer can apply for FDA approval. It’s a 400 mg tablet taken by mouth once daily, but can be reduced to a lower dosage of 300 mg or 200 mg in people who have serious side effects.
This study found that elacestrant may work better than some other breast cancer medications. It increased the amount of time without seeing cancer growth compared to an AI or fulvestrant in people with advanced ER-positive/HER-2 negative breast cancer. HER2 is a protein found on some breast cancer cells that also contributes to cancer growth.
Aside from elacestrant, many other oral SERDs are in various stages of development.
| Medication name | Current study phase |
| Camizestrant (AZD9833) | Phase 3 |
| Giredestrant (GDC-9545) | Phase 3 |
| Imlunestrant (LY3484356) | Phase 3 |
| Rintodestrant (G1T48) | Phase 1 |
| Borestrant (ZB-716) | Phase 1/2 |
| ZN-c5 | Phase 1/2 |
| D-0502 | Phase 1 |
| SCR-6852 | Phase 1 |
Amcenestrant was being studied in a phase 3 clinical trial in combination with palbociclib (Ibrance). However, investigators stopped the trial early due to effectiveness concerns. Amcenestrant is no longer being developed.
How long will it be until oral SERDs are widely available for breast cancer?
There’s a chance the first oral SERD may be approved in the near future. The company that makes elacestrant has submitted an application to the FDA to review their medication for approval. The FDA granted this medication a priority review, and they’re scheduled to review the application by February 2023. That’s likely the earliest we’d see any oral SERDs available for use.
Other oral SERDs, such as camizestrant, girdestrant, or imlunestrant, may be approved in the future. But they aren’t as far along in the development process compared to elacestrant.
What are the biggest obstacles to oral SERD approval for breast cancer?
Right now, the biggest obstacle is seeing if oral SERDs are better than other medications used to treat ER-positive breast cancer. Side effects are another consideration.
One oral SERD being developed has already been pulled from development due to effectiveness concerns. And other SERDs — with the exception of elacestrant — still need to prove their safety and effectiveness in clinical trials before they can apply for FDA approval. If and when the FDA accepts their submissions, it can take up to 10 months to review their applications.
Researchers also need to make sure that the new oral SERDs don’t cause intolerable side effects. It doesn’t matter if a new medication is more effective if people can’t tolerate it.
The bottom line
Oral SERDs are a potential new option for people with ER-positive breast cancer. Even though oral SERDs aren’t FDA approved yet, elacestrant’s recent study suggests that it may be safe and effective for people with ER-positive/HER2 negative breast cancer. Its FDA approval could come by February 2023.
Why trust our experts?
References
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