For many people diagnosed with estrogen receptor–positive (ER-positive), HER2-negative advanced breast cancer, hormone (endocrine) therapy is an essential part of treatment. These therapies work by blocking estrogen or stopping it from stimulating cancer growth. While treatments such as aromatase inhibitors, tamoxifen, and CDK4/6 inhibitors can be very effective, most cancers eventually find ways to grow again, even with treatment.
Because of this, researchers continue to develop new medicines that can better control hormone-driven breast cancer after standard therapies stop working. One of the most promising new drugs being studied today is vepdegestrant, also known as ARV-471.
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What Is Vepdegestrant?
Vepdegestrant is an oral (pill-based) hormone therapy designed for people with ER-positive, HER2-negative advanced or metastatic breast cancer. It is still considered an investigational medicine, meaning it is being studied in clinical trials and is not yet approved for routine use.
Unlike some existing treatments that block the estrogen receptor, vepdegestrant is designed to remove the estrogen receptor entirely from cancer cells. This approach may help stop cancer growth more effectively, especially when the cancer has become resistant to other hormone therapies.
How Does Vepdegestrant Work?
Breast cancers that are ER-positive depend on the estrogen receptor to grow. Many current treatments try to block estrogen or interfere with how the receptor works. Over time, however, cancer cells can adapt, including by changing the structure of the estrogen receptor itself.
Vepdegestrant uses a newer scientific approach called targeted protein degradation. Instead of just blocking the estrogen receptor, the drug marks it for destruction inside the cell, so it is broken down and removed. This may be especially helpful for cancers that carry ESR1 mutations, which are a common cause of resistance after aromatase inhibitor therapy (ClinicalTrials.gov, VERITAC-2).
Because vepdegestrant is taken by mouth once daily, it may also be more convenient than treatments like fulvestrant, which require regular injections.
Who Is Vepdegestrant Being Studied For?
Vepdegestrant is currently being studied in people who:
- Have ER-positive, HER2-negative advanced or metastatic breast cancer
- Have cancer that has returned or spread and cannot be cured with surgery or radiation
- Have already been treated with a CDK4/6 inhibitor plus hormone therapy
- May have received one additional hormone therapy for advanced disease
This reflects a very common real-world situation, as CDK4/6 inhibitors are now standard first-line treatment for many patients with advanced ER-positive breast cancer.
What Is the VERITAC-2 Trial?
The main study evaluating vepdegestrant is called VERITAC-2, a large Phase 3 clinical trial. In this study, patients are randomly assigned to receive either:
- Vepdegestrant (oral, once daily)
or - Fulvestrant, a commonly used injectable hormone therapy
The goal of the trial is to determine whether vepdegestrant can keep cancer from worsening for longer than fulvestrant. The main outcome being measured is progression-free survival, which means how long patients live without their cancer getting worse, based on regular imaging scans reviewed by independent experts (ClinicalTrials.gov, VERITAC-2).
The study also looks at overall survival, tumor response, side effects, and quality of life, including pain, daily functioning, and overall well-being.
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Are There Results Yet?
As of now, final results from the VERITAC-2 trial have not been published. This means doctors do not yet know whether vepdegestrant works better than fulvestrant in this setting. The study is ongoing, and results are expected once enough events (such as cancer progression) have occurred to allow a reliable comparison.
It is important for patients to understand that while vepdegestrant is promising, it is not yet proven to be better than existing treatments outside of clinical trials.
What About Side Effects?
Because vepdegestrant is still being studied, doctors are continuing to learn about its full side-effect profile. So far, safety monitoring in clinical trials includes:
- General side effects related to hormone therapy
- Laboratory changes
- Heart rhythm monitoring (ECG)
- Ongoing assessment of how patients feel and function day to day
One important part of the VERITAC-2 trial is the careful evaluation of quality of life, recognizing that long-term treatment should control cancer without significantly disrupting daily living.
Why This Drug Matters
If vepdegestrant proves effective, it could become an important new option for people whose breast cancer has stopped responding to current hormone therapies. Its ability to remove the estrogen receptor entirely may help overcome common resistance mechanisms and provide longer disease control.
In addition, its oral administration could offer a more convenient alternative to injectable therapies, which can be burdensome over time.
What Should Patients Do Now?
If you have ER-positive, HER2-negative advanced breast cancer and your disease has progressed after CDK4/6 inhibitor therapy, it may be worth discussing clinical trial options with your oncologist. Trials like VERITAC-2 help answer important questions and may provide access to promising new treatments before they are widely available.
Key Takeaway
Vepdegestrant (ARV-471) is a next-generation hormone therapy designed to eliminate the estrogen receptor, rather than simply block it. While it is still under investigation, it represents a hopeful new direction for treating hormone-resistant breast cancer. Ongoing clinical trials will determine whether it becomes a future standard treatment option.
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Written by Armen Gevorgyan, MD