This approval affects oncologists, breast cancer specialists, and other clinicians who manage adults with ER-positive, HER2-negative advanced or metastatic breast cancer harboring ESR1 mutations detected by an FDA-authorized test. The VERITAC-2 data support selecting vepdegestrant for patients with ESR1‑mutated tumors after progression on at least one prior endocrine therapy, including prior CDK4/6 inhibitor therapy, based on improved PFS and higher ORR versus fulvestrant in that subgroup. How will clinicians integrate routine plasma ctDNA testing for ESR1 mutations into workflow to identify eligible patients and time sequencing with other available therapies?

Q1 What is vepdegestrant (Veppanu) approved for?

Vepdegestrant (Veppanu) is approved for the treatment of adults with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, ESR1‑mutated advanced or metastatic breast cancer, as detected by an FDA-authorized test, with disease progression following at least one line of endocrine therapy. The indication requires ESR1 mutation detection by an FDA-authorized companion diagnostic prior to treatment.

Q2 How does vepdegestrant work?

Vepdegestrant is described in the approval and published summaries as a heterobifunctional protein degrader (a PROTAC-like modality) that targets the estrogen receptor pathway to induce degradation of the receptor protein. Regulatory summaries and peer-reviewed accounts state the agent recruits an E3 ligase to the estrogen receptor, promoting ubiquitination and proteasomal degradation of the receptor protein.

Q3 What is the recommended dose of vepdegestrant (Veppanu)?

The recommended dosage of Veppanu is 200 mg taken orally once daily with food until disease progression or unacceptable toxicity, per the prescribing information. The label provides dose-reduction guidance (100 mg once daily) and specific instructions for handling drug interactions with strong CYP3A inhibitors or inducers and for QTc-related dose modifications. Clinicians should consult current prescribing information for complete dosing guidance.

Q4 What are the side effects of vepdegestrant?

The label lists the most common adverse reactions (≥10%) as decreased white blood cells, increased AST, musculoskeletal pain, fatigue, decreased hemoglobin, decreased neutrophils, increased ALT, increased alkaline phosphatase, nausea, decreased blood potassium, increased bilirubin, decreased appetite, electrocardiogram QT prolonged, decreased platelets, and constipation. QTc interval prolongation was observed in 10% of patients in VERITAC-2, with Grade 3 QTc events in 1.6% and QTc >500 msec in 1.6% of patients; serious adverse reactions occurred in 9% and fatal adverse reactions in 1.0% of patients.

Clinicians should consult current prescribing information for complete dosing guidance.