Oncologists and breast cancer specialists managing adults with ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer and those treating HER2-positive early-stage breast cancer will need to integrate these newly FDA-approved options into patient selection and testing workflows, including use of an FDA-authorized ESR1 test for vepdegestrant and FDA-authorized HER2 assays for ENHERTU ^[3][4][1]. The VERITAC-2 results support vepdegestrant as an oral option versus fulvestrant in patients with ESR1 mutations after prior endocrine therapy, and DESTINY-Breast11 supports neoadjuvant T-DXd followed by THP and an adjuvant ENHERTU indication for patients with residual invasive disease after neoadjuvant therapy ^[3][4][6]. Will overall survival benefit and longer-term safety data for these new indications be confirmed with continued follow-up and postapproval studies?

Q1 What is vepdegestrant (Veppanu) approved for?

A1 Vepdegestrant (Veppanu) is approved for adults with estrogen receptor (ER)-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer whose disease progressed following at least one line of endocrine therapy. The FDA approval includes use of an FDA-authorized companion diagnostic (Guardant360 CDx) to identify ESR1 mutations for patient selection. The approval was based on VERITAC-2 data showing improved progression-free survival in the ESR1-mutant population.

Q2 How does vepdegestrant work?

A2 The FDA describes vepdegestrant as a heterobifunctional protein degrader. In VERITAC-2 it was evaluated as an oral protein degrader targeting the estrogen receptor pathway in ER-positive breast cancer; the application and review materials characterize the agent and its mechanism as a degrader of the target protein leading to antitumor activity in ESR1-mutated tumors.

Q3 What is the recommended dose of vepdegestrant (Veppanu) and of ENHERTU in the newly approved indications?

A3 The recommended vepdegestrant dose approved by the FDA is 200 mg taken orally once daily with food until disease progression or unacceptable toxicity. ENHERTU dosing in the updated prescribing information varies by indication; for many breast cancer indications ENHERTU is dosed at 5.4 mg/kg every 3 weeks, with specific regimens for neoadjuvant and adjuvant use described in the label. Clinicians should consult current prescribing information for complete dosing guidance.

Q4 What are the most common side effects of vepdegestrant and ENHERTU?

A4 Vepdegestrant labeling includes warnings and precautions for QTc interval prolongation and embryo-fetal toxicity; the FDA communication highlights these safety considerations. ENHERTU carries boxed warnings for interstitial lung disease and embryo-fetal toxicity and additional labeled warnings for neutropenia and left ventricular dysfunction; the ENHERTU label lists common adverse reactions (≥20%) such as decreased white blood cell count, nausea, decreased hemoglobin, decreased neutrophil count, decreased lymphocyte count, fatigue, decreased platelet count, increased transaminases, vomiting, alopecia, constipation, decreased potassium, decreased appetite, diarrhea, and musculoskeletal pain.