The U.S. Food and Drug Administration has approved vepdegestrant (Veppanu), a novel heterobifunctional protein degrader, for adults with estrogen receptor (ER)-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer. The approval applies to patients whose disease has progressed after at least one line of endocrine therapy, with ESR1 mutations confirmed through an FDA-authorised test.
Companion Diagnostic Approved for Targeted Treatment
Alongside the drug approval, the FDA has also cleared the Guardant360 CDx as a companion diagnostic. This test enables clinicians to identify patients with ESR1 mutations who are most likely to benefit from vepdegestrant, thereby supporting a more personalised treatment approach.
Clinical Trial Demonstrates Improved Outcomes
As per the press release, the approval is based on findings from the VERITAC-2 (NCT05654623) trial, a randomised, open-label, multicentre study involving 624 adults with ER-positive, HER2-negative advanced or metastatic breast cancer. Among these, 270 patients had tumours carrying ESR1 mutations.
Patients had previously experienced disease progression after one or two lines of endocrine therapy, including treatment with a CDK4/6 inhibitor. Researchers randomised participants to receive either oral vepdegestrant once daily or intramuscular fulvestrant at scheduled intervals.
Notably, in patients with ESR1-mutated tumours, vepdegestrant demonstrated a statistically significant improvement in progression-free survival (PFS). Median PFS reached 5 months in the vepdegestrant group compared to 2.1 months in the fulvestrant group. Moreover, the objective response rate (ORR) was higher with vepdegestrant (19%) versus fulvestrant (4%).
Ongoing Evaluation of Overall Survival
Although the study showed promising efficacy results, overall survival (OS) data remain immature. At the time of analysis, only 16% of deaths had occurred in the ESR1-mutated population, and further follow-up is ongoing to determine long-term survival benefits.
Safety Profile and Key Precautions
The prescribing information highlights important safety considerations. Specifically, clinicians should monitor for QTc interval prolongation and potential embryo-fetal toxicity. Therefore, careful patient selection and monitoring remain essential during treatment.
Dosage and Administration
As per the FDA, the recommended dose of vepdegestrant is 200 mg taken orally once daily with food. Patients should continue treatment until disease progression or the development of unacceptable toxicity.
Advancing Precision Oncology
With this approval, the FDA reinforces the role of targeted therapies and companion diagnostics in advancing precision oncology. By integrating molecular testing with tailored treatments, clinicians can improve outcomes for patients with advanced breast cancer.