FDA Approves Vepdegestrant for ER-Positive, HER2-Negative, ESR1-Mutated Advanced or Metastatic Breast Cancer

On May 1, 2026, the FDA approved vepdegestrant (Veppanu), a heterobifunctional protein degrader, for adults with estrogen receptor (ER)–positive, human epidermal growth factor receptor 2 (HER2)–negative, ESR1-mutated advanced or metastatic breast cancer, as identified by an FDA-authorized test, following disease progression after at least 1 line of endocrine therapy.¹

The FDA also approved the Guardant360 CDx as a companion diagnostic to detect ESR1 mutations, supporting patient selection for treatment with vepdegestrant.¹ For oncology nurses, this reinforces the importance of coordinating biomarker testing, including circulating tumor DNA (ctDNA), and ensuring results are documented and acted on in a timely manner to guide treatment decisions.

VERITAC-2 Trial Results: Progression-Free Survival and Response Rates

Approval was based on results from the phase 3 VERITAC-2 trial (NCT05654623), which enrolled 624 patients with ER-positive, HER2-negative advanced or metastatic breast cancer, including 270 with ESR1-mutated tumors.¹ Patients had disease progression following 1 to 2 prior lines of endocrine therapy, including a CDK4/6 inhibitor.¹

Patients were randomly assigned to receive oral vepdegestrant once daily or intramuscular fulvestrant.¹ The oral administration of vepdegestrant may reduce injection-related visits, but shifts responsibility to patient adherence, making nurse-led education and follow-up critical.

Among patients with ESR1-mutated disease, vepdegestrant significantly improved progression-free survival (PFS) compared with fulvestrant.¹ Median PFS was 5.0 months (95% CI, 3.7-7.4) vs 2.1 months (95% CI, 1.9-3.5), respectively (hazard ratio, 0.57; 95% CI, 0.42-0.77; P = .0001).¹

The objective response rate (ORR) was 19% with vepdegestrant vs 4% with fulvestrant.¹ Overall survival data remain immature.¹

Oral Administration and Adherence: What Oncology Nurses Should Know

Vepdegestrant is administered at 200 mg orally once daily with food until disease progression or unacceptable toxicity.¹ Nurses should counsel patients on consistent daily dosing with food, missed dose management per prescribing information, and the importance of adherence to maintain therapeutic benefit.

Because this is an oral therapy, nurses may need to implement adherence strategies such as medication calendars, follow-up calls, and coordination with specialty pharmacies. Assessing barriers such as cost, access, and patient understanding is essential.

Safety Profile: Monitoring for QTc Prolongation and Embryo-Fetal Toxicity

The prescribing information includes warnings for QTc interval prolongation and embryo-fetal toxicity.¹ Nurses should monitor for risk factors associated with QTc prolongation, review concomitant medications that may increase risk, and support appropriate electrocardiogram monitoring when indicated.

Patient education should include counseling on signs and symptoms that warrant prompt reporting, as well as reinforcement of effective contraception for patients of reproductive potential due to embryo-fetal risk.¹

Biomarker Testing and Care Coordination in ESR1-Mutated Breast Cancer

This approval highlights the growing role of ESR1 mutation testing in treatment selection. Oncology nurses are often central to coordinating liquid biopsy testing, tracking results, and facilitating timely treatment initiation. Ensuring clear communication between the care team and patients about test results and next steps is critical to avoid delays in therapy.

Reference

1. US Food and Drug Administration. FDA approves vepdegestrant for ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer. May 1, 2026. Accessed May 1, 2026.