By Nisha Unni, MD, as told to Stephanie Booth
Nisha Unni, MD, is an oncologist at UT Southwestern Medical Center who specializes in breast cancer. The information here represents her knowledge and experience as a medical professional.
In May 2026, the FDA approved vepdegestrant (Veppanu) to treat breast cancer that’s estrogen receptor (ER) positive, human epidermal growth factor receptor 2 (HER2) negative, and ESR1-mutated advanced. It can also be prescribed for metastatic breast cancer that’s progressed after at least one line of endocrine therapy.
Vepdegestrant is a selective estrogen receptor degrader (SERD). This class of drugs works by breaking down the estrogen receptors inside your cells and also making it harder for estrogen to bind to them. That keeps cancer cells from using estrogen to grow.
Alongside vepdegestrant, the FDA approved a liquid biopsy (blood) test, the Guardant360 Liquid CDx, that can look for ESR1 biomarkers. Your results can help your doctor understand if vepdegestrant may help treat your cancer.
Below, Nisha Unni, MD, an oncologist at UT Southwestern Medical Center in Dallas, Texas, who specializes in breast cancer, explains what sets vepdegestrant apart from other SERDs and how it could help you.
Who typically benefits from this treatment?
Vepdegestrant is approved for patients with locally advanced or advanced-stage metastatic hormone receptor-positive and HER2-negative breast cancers whose tumor carries a particular mutation called ESR1 and who have progressed on at least one line of treatment. It can be any line. It can be as simple as an antihormonal therapy that you got, and now your cancer is not responding to that treatment. That's the FDA label for the approval of this drug.
The clinical significance of ESR1 mutations has only been recognized relatively recently. It's a gene that codes for the estrogen receptor. Usually, the receptor stays open in an off form, and estrogen binds to it and turns on the switch. Antihormonal agents come and attach to it, then close the receptor. When there is a mutation, the receptor stays open permanently. It doesn’t depend on estrogen, so this makes antihormonal therapies ineffective. And that’s where these newer agents, SERDs, come into play.
What sets this treatment apart from others?
It’s a slightly different agent than the previously approved oral SERDs. It’s a first-in-class oral agent, which is also a PROTAC, which stands for PROteolysis TArgeting Chimera. It's a protein degrader, so it's actually a very reusable tool. The molecule tags one protein target for destruction, then releases the drug or the molecule, and that molecule or drug moves on to tag another protein. It repeats the same process, and this goes on and on.
This is something that a conventional drug is not able to do because it stays attached to one target all the time.
These agents are now being used in multiple scenarios, but vepdegestrant is the first PROTAC approved in breast cancer.
Can you tell me about how well this treatment works and how quickly patients might see results?
The old-fashioned SERD is called fulvestrant (Faslodex). It's an oil-based injection. People have two at the same time into the muscle, one after the other, and they're just not a pleasant feeling, especially when you have to get it regularly. Vepdegestrant is a better drug than the traditional Faslodex. That's what [the clinical trial] showed. And it's an oral pill, so it's a win-win.
How long did it take to see a response [in trials]? That's a little tricky because, first of all, we don't have those results, which are called “time to response.” But what I can say is that there's something called “objective response rate.” That's a fancy way of saying what percentage of patients whose tumors responded to one treatment versus the other.
For the people who took vepdegestrant, their objective response rate was 19% compared to only 4% in the fulvestrant group.
This is very early data, and we will continue to see other data hopefully with time. For instance, one of our gold standards in any cancer trials is “overall survival.” We don’t yet have that from this trial because it takes more time to get reported.
Is this treatment generally considered safe?
Generally speaking, vepdegestrant is well tolerated. Sometimes I think we clinicians tend to overuse that term, but the main side effect reported in the trial was fatigue, which is important, but it didn't have to be debilitating fatigue. Some grade of fatigue was seen in about 29% of patients.
We didn't see a lot of discontinuation rates or dose reductions. That means how many people went off vepdegestrant because they couldn’t tolerate it and how many people had to dose reduce because they couldn’t tolerate the full dose or a dose that they were on. That was very low.
The discontinuation rate was 3%. That tells a lot to us.
What sort of side effects can people expect, and are there ways to handle them?
Other than fatigue, we have to monitor liver function. It can be a little elevated in some people. Some people also have nausea, constipation, but there’s less incidence of vomiting [a side effect that we see with other SERDs], which is very important.
The whole idea of having an oral medication is to keep some semblance of normalcy in your life. That's what we’re striving to achieve especially in estrogen-positive, advanced, and metastatic breast cancer by keeping more and more treatments oral and very manageable at home.
We can give you a cocktail of oral nausea medications to help prevent or manage the nausea. Being proactive is key. There are many different reasons to feel fatigued, and we’ll work together to figure out if anything else could be contributing in your case. We do encourage you to eat well, sleep well, reduce stress, and exercise. Massage therapy, sleep, therapy, acupuncture — we try to incorporate all these things in addition to the medications we prescribe.
How do you take this treatment, and will people need any regular tests or checkups?
Vepdegestrant is a once-a-day pill.
Every medication comes with its own regular tests and checkups. For vepdegestrant, we do an EKG or ECG prior to starting the drug. We want to make sure that your QT interval [the time it takes your heart to contract and recover] is within a certain range before we start. A lot of these medications, including vepdegestrant, can prolong it. We have to make sure that it’s not already long to begin with because there are conditions like congenital QT syndrome. A prolonged QT interval means the heart’s electrical system is taking longer than normal to reset, which can sometimes lead to a dangerous abnormal heart rhythm.
Also, you may be taking different medications that already prolong the QT interval. We don't want to cause interactions with other medications and prolong it even more.
You’ll need a repeat EKG or ECG about four weeks after starting vepdegestrant. If those two values look good, then [additional EKG testing] is based on symptoms and any concerns from your medical team. If there are other concerns, like you already had a borderline QT interval, electrolyte abnormalities, or if you add any medication that might prolong the QT, then we increase the frequency of monitoring your EKG.
We also have to make sure that your electrolytes are well-balanced and monitored and correct any electrolyte abnormalities. Your potassium, magnesium, and other tests like metabolic panel and blood count have to be looked at, usually prior to starting and at regular intervals.
Are there any types of people who shouldn't take this treatment, like those with certain health conditions or who are taking other medications?
There are no absolute contraindications [medical reasons for anyone to avoid the treatment] that are listed, but we need to be careful about EKG abnormalities. Vepdegestrant can also cause fetal harm, like many medications. We generally counsel you not to get pregnant [while on it]. Breastfeeding should be avoided during treatment and for two weeks after the last dose.
How much does this treatment cost? Will insurance cover it, or are there options for financial assistance?
Like any new newly approved therapy, Vepdegestrant is costly, but the price can also vary significantly depending on your insurance coverage.
Most new drugs, especially oral ones, have multiple options for financial assistance, like manufacturer patient assistance programs, and copay cards, which can cover out-of-pocket expenses. Sometimes free drug programs are available if you’re underinsured and meet a certain income.
You may always explore nonprofit foundations, which can help with copay, travel, and related expenses. Institutions like ours offer financial assistance and counselors, and our pharmacy staff are well-versed in proactively working to secure coverage and identify programs.
How can people find out more about whether this treatment would be a good fit for them?
If it hasn’t been done already, bring up with your doctor about testing the cancer cells for ESR1 mutations. It's a simple blood test called a liquid biopsy. It doesn’t have to be a new tumor biopsy. In fact, liquid biopsies are preferred for ESR1 mutations. It's easier, less invasive.
If the test is positive for that mutation, and you’ve already tried one form of endocrine-based therapy, ask whether vepdegestrant is an option, but discuss it alongside other options in the same treatment category. There are several new and similar drugs that are now available.
It also depends on your other risk factors and medical history. Your doctor will be the best person to pick the best fit for you.
Vepdegestrant's website has information for both patients and physicians.
Can you give me some insights into the research and studies behind this treatment?
A 2025 phase 3 global study enrolled more than 600 patients. It was a very well-balanced study: Randomized people got either vepdegestrant versus the traditional injectable, fulvestrant.
Of the 270 patients with an ESR1 mutation, there was an improvement in what we call median progression-free survival (PFS). That’s a fancy way of saying how long the treatment kept a disease like cancer from getting worse. Compared to the standard of care for fulvestrant, it more than doubled. Vepdegestrant had a median PFS of five months. For fulvestrant, it was only two months.
Now that may not look like much, but it’s a 43% improvement … which is great in our book for an oral pill that has fewer side effects and is easier to tolerate.
Vepdegestrant was approved only in ESR1 mutated patients versus patients with the wild type, who don't carry that particular mutation. Those are people who probably benefited from the old-fashioned way of doing things, like fulvestrant, and they didn't have the mutation, so they necessarily didn't need this mechanism to keep the cancer under control.
There are many trials using vepdegestrant, especially in combination with other agents. That's where the science is heading: combining oral SERDs with other agents to improve how well it works. I always tell my patients that there are many options and therapies on the horizon that are in trials.
It's just a very exciting time to be in oncology. And from a patient perspective, it’s a great outlook. You can enroll in trials and when they become fruitful and these drugs get approved, you can be part of that success story as well.
