FDA Approves Veppanu for ESR1+ Metastatic Breast Cancer

The U.S. Food and Drug Administration (FDA) has approved Veppanu (vepdegestrant), marking a significant milestone in the treatment of adults with advanced or metastatic breast cancer harboring ESR1 mutations. The agency announced the approval in a news release issued Friday.

The approval specifically targets patients with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative tumors that have progressed after at least one line of endocrine therapy. Developed by Arvinas Operations, Inc., Veppanu represents a new class of therapy known as a heterobifunctional protein degrader.

Alongside the drug’s approval, the FDA also cleared the Guardant360 CDx as a companion diagnostic device. This liquid biopsy test will be used to identify patients whose tumors carry the ESR1 mutation, a common resistance mechanism that develops during prior endocrine treatments.

Breaking resistance in advanced disease

For many patients with ER-positive breast cancer, the ESR1 mutation acts as a biological on-switch, allowing the cancer to grow even when traditional hormone therapies attempt to block estrogen. Veppanu works by targeting and breaking down the estrogen receptor protein itself, rather than simply blocking it.

The FDA’s decision was bolstered by results from the VERITAC-2 clinical trial, a randomized, multicenter study involving 624 adults. Within this group, 270 patients had confirmed ESR1 mutations. All participants had previously seen their disease progress on one or two prior lines of endocrine therapy, including mandatory prior treatment with a CDK4/6 inhibitor.

Patients were randomized to receive either 200 mg of oral Veppanu daily or intramuscular injections of Faslodex (fulvestrant), which is the current standard-of-care treatment.

Trial results: Doubling of progression-free survival

In the patient population with ESR1 mutations, Veppanu demonstrated a statistically significant improvement in progression-free survival (PFS), or length of time a patient lives with the disease without it getting worse or spreading.

According to the data:

• Median PFS: Patients taking Veppanu saw a median PFS of five months, compared to 2.1 months for those on Faslodex.
• Risk Reduction: The treatment reduced the risk of disease progression or death by 43%.
• Response Rate: The objective response rate (ORR) was 19% for the Veppanu group, nearly five times higher than the 4% seen in the Faslodex arm.

While overall survival data remained immature at the time of analysis, with only 16% of deaths recorded, the clinical benefit in PFS and response rates provided a clear path for the drug's entry into the oncology armamentarium.

Safety and administration

The FDA noted in the news release that the recommended dose for vepdegestrant is 200 mg, taken orally once daily with food. Treatment should continue until disease progression or unacceptable toxicity occurs.

The drug’s prescribing information includes important warnings and precautions regarding:

1. QTc Interval Prolongation: A potential heart rhythm condition that requires monitoring.
2. Embryo-Fetal Toxicity: The drug may cause harm to a developing fetus and patients of reproductive potential are advised to use effective contraception.

A new tool for the metastatic community

The approval of Veppanu offers a potent new oral option for a patient population that often faces dwindling choices once resistance to initial hormone therapies develops. By utilizing a protein degrader approach, clinicians hope to more effectively clear the path for long-term disease management in the metastatic setting.

Full prescribing information for Veppanu is expected to be available shortly on the FDA’s official website.

Editor's note: This article is for informational purposes only and is not a substitute for professional medical advice, as your own experience will be unique. Use this article to guide discussions with your oncologist. Content was generated with AI, reviewed by a human editor, but not independently verified by a medical professional.

Reference

“FDA approves vepdegestrant for ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer,” FDA news release.