By Madhurima Anne, MD, as told to Stephanie Booth
Madhurima Anne, MD, is an oncologist at Hackensack Meridian Health Jersey Shore University Medical Center and Ocean University Medical Center in Neptune, New Jersey. The information here represents her knowledge and experience as a medical professional.
Fulvestrant (Faslodex) is a type of breast cancer treatment known as a selective estrogen receptor degrader (SERD). Drugs in this class are used to treat breast cancer that relies on estrogen to spread and grow. SERDs prevent estrogen from binding to receptors inside of the cancer cells in your breast tissue. They also change how well these receptors function.
Your doctor may prescribe fulvestrant as a first-line treatment if you’ve been diagnosed with advanced-stage, hormone receptor-positive, HER2-negative breast cancer and have been through menopause. It can also be an option if a different hormone therapy drug doesn’t work well for you.
Over two decades ago, fulvestrant was the first SERD to be approved by the FDA. At the time, studies showed that it was just as effective as chemotherapy in treating breast cancer while doing a better job of preserving quality of life. A newer generation of SERDs includes treatments that are more convenient and are better absorbed by your body, but fulvestrant can still be part of an effective treatment plan.
We spoke to Madhurima Anne, MD, an oncologist at Hackensack Meridian Health Jersey Shore University Medical Center and Ocean University Medical Center, about how fulvestrant works and what else you need to know about this treatment.
Who typically benefits from this treatment?
Fulvestrant was initially approved for women with stage IV metastatic breast cancer who have been on an anti-hormone pill that's no longer working for them. Now, it’s a first-line treatment for metastatic breast cancer, for single-agent use, as well as in combination with other therapies.
Doctors are also adding fulvestrant onto other sorts of targeted therapies for metastatic breast cancer. It helps to maximize your anti-estrogen outcome.
What sets it apart from other treatments?
Fulvestrant is an estrogen receptor antagonist used in people with breast cancer cells that express hormone receptors (estrogen/progesterone receptors). It’s a selective estrogen receptor degrader, or SERD. Fulvestrant competitively goes in and binds onto the estrogen receptor, which is expressed on those breast cancer cells that overexpress estrogen. The estrogen that’s stimulating those cancer cells then can't bind to those receptors. That's one mechanism.
The other mechanism is that it causes the estrogen receptors to degrade and slowly disappear so there are less of them present on the breast cancer cells.
There are oral SERDs that work better and are fancier than Faslodex. But they're not approved for use in the way that Faslodex is approved. The newer SERDs, such as vepdegestrant (Veppanu), are only approved for patients who have a specific ESR1 mutation in the metastatic setting.
When did this treatment become available?
Fulvestrant was first approved in 2002 for treatment of hormone receptor-positive metastatic breast cancer that became resistant to oral antiestrogen therapies, such as tamoxifen and aromatase inhibitors. It was approved at a dose of 250 milligrams each month based on trials showing that it worked as well as aromatase inhibitors. It’s now used at the higher dose of 500 milligrams each month.
How well does this treatment work and how quickly can patients see results?
It depends on the person and how many prior therapies you’ve had. It's really variable. Unlike chemotherapy, fulvestrant tends to work slower, but you can generally see efficacy after three months.
There's no blood test [to see how well Faslodex is working]. Instead, your doctor can do measurement of tumors by physical exam or look at serial CAT scans or PET scans.
Is this treatment generally considered safe?
It is generally well-tolerated and tends to be better tolerated than other antiestrogen therapies like tamoxifen and aromatase inhibitors.
How do you take it, and will people need any regular tests or checkups?
Fulvestrant is given as two intramuscular (IM) injections, one in each buttock, with a loading dose of every 15 days for three doses (day 0, 15, 29) for the first month, followed by every 28-day administration.
Because it is an injection, it’s usually administered in a [doctor’s] office or infusion center.
Fulvestrant can be continued indefinitely as long as you’re tolerating, and responding to, treatment or at the discretion of your doctor.
[While you’re taking fulvestrant], you should have your liver function tests monitored. If you have preexisting liver dysfunction, you may be safer with the lower dose of fulvestrant (250 milligrams). If you’re of childbearing age, pregnancy tests are recommended prior to starting, and you’re recommended to be on birth control and to avoid pregnancy while on it.
Everyone on hormonal therapies such as fulvestrant needs to be counseled on their increased risk of cardiovascular disease. Follow up with your primary care doctor for routine blood pressure, cholesterol, and diabetes screenings.
What sort of side effects can people expect from this treatment, and are there ways to handle them?
There’s often pain at the injection site. [Each injection takes one to two minutes.]
Fulvetrant has to be refrigerated, so when you take it straight out of the fridge and you try to inject it, because it's so thick and you're doing this intramuscular push, it hurts more. If the nurse takes it out earlier and allows it to get to room temperature, it's less thick and tends to be a little bit more tolerable. You could ask for some topical lidocaine cream before it’s injected. Then, immediately after the injection, apply a cold or warm compress.
I haven’t had people discontinue fulvestrant because of [the pain of the shot]. It’s pretty tolerable.
Other side effects include fatigue, bone pains, muscle aches, hot flashes, nausea, vomiting, constipation, diarrhea, and abdominal pain.
Are there any people who shouldn't take this treatment, like those with certain health conditions or who are taking other medications?
Fulvestrant can cause fetal harm when given to pregnant women. And because it’s given as an intramuscular injection, fulvestrant should be used with caution if you have a bleeding disorder, low platelets, or are on blood thinners.
How much does it cost? Will insurance cover it, or are there options for financial assistance?
It costs about $2,000 a month. However, everyone should check with their insurance companies for their out-of-pocket cost. [Fulvestrant’s manufacturer, AstraZeneca, also has a patient assistance program.]
Generic fulvestrant is available, which may lower the cost.
How can people find out more about whether this treatment would be a good fit for them?
The National Cancer Institute is a good place to read about fulvestrant. Then, have a discussion with your doctor. I would suggest that everyone with stage IV breast cancer undergo next-generation sequencing of your blood or tumor to look for targetable mutations, then have a conversation with your doctor about what your appropriate first-line therapy should be.
Are there any major studies worth commenting on?
- In 2010, based on trials showing greater anti-tumor activity with higher doses, a new 500 milligram/month dose of fulvestrant was approved.
- In 2017, based on the results of the Phase III FALCON trial, fulvestrant received approval for use as a first-line therapy in postmenopausal patients with hormone receptor-positive metastatic breast cancer.
- Also in 2017, fulvestrant received approval for use in combination with a CDK 4/6 inhibitor, abemaciclib, in patients with hormone receptor-positive metastatic breast cancer based on the results of the MONARCH 2 trial. [CDK 4/6 inhibitors target specific proteins, cyclin-dependent kinases 4 and 6, that help cancer cells grow and spread.]
Fulvestrant is a drug we can't forget about. But I think in the next couple of weeks to months, we're going to start to see a whole lot of drug approvals. That’s because we want the best for our patients.
