Vepdegestrant FDA Approval: What to Know About the First Breast Cancer PROTAC

On May 1, the FDA granted approval to vepdegestrant (Veppanu), marking a significant milestone as the first-ever proteolysis-targeting chimera (PROTAC) for cancer treatment.

This novel therapy is indicated for adult patients with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, ESR1-mutated advanced or metastatic breast cancer that has progressed after at least one line of endocrine therapy.

For the oncology nursing community, understanding the unique mechanism of this drug, its specific administration requirements, and its safety profile is essential for optimizing patient outcomes and adherence. To gain insight into these nursing priorities, Oncology Nursing News spoke with Dr. Komal Jhaveri, an investigator in the pivotal VERITAC-2 trial and a medical oncologist at Memorial Sloan Kettering Cancer Center.

A new tool against endocrine resistance

Vepdegestrant targets the ESR1 mutation, a common mechanism of resistance where breast cancer cells continue to grow despite estrogen suppression. Unlike traditional inhibitors that simply block the receptor, vepdegestrant is a heterobifunctional protein degrader.

As Jhaveri explains, the drug works by binding to both the estrogen receptor and a U3 ligase, which triggers the proteasomal degradation of the receptor. In the VERITAC-2 trial, this mechanism translated to a significant clinical benefit: patients with ESR1 mutations saw a median progression-free survival (PFS) of 5 months with vepdegestrant, compared to 2.1 months with the standard-of-care fulvestrant (Faslodex).

Nursing priorities: Administration and monitoring

Vepdegestrant is an oral medication administered at a dose of 200 mg once daily. Nurses should emphasize that the drug must be taken with food to ensure proper absorption and efficacy.

Before starting treatment, nurses must confirm the patient’s ESR1 status via an FDA-authorized test. The Guardant360 CDx was approved as a companion diagnostic to identify these mutations using central or local testing of circulating tumor DNA (ctDNA).

Managing the side effects

Jhaveri identified the primary adverse events for nurses to monitor as fatigue, nausea and musculoskeletal pain. While these side effects occurred in the trial, she noted they were predominantly low-grade and rarely led to treatment discontinuation.

The role of the oncology nurse is critical in managing these symptoms at home. “I think it's all about education and communication,” Jhaveri told Oncology Nursing News. She stressed that nurses, as frontline providers, must bridge the gap by reminding patients to report these symptoms early. Supportive management and, if necessary, dose modifications can prevent patients from discontinuing the drug prematurely.

Safety warnings: QTc prolongation

One specific safety concern highlighted in the FDA label is the risk of QTc interval prolongation. Nurses play a vital role in coordinating the required cardiac monitoring.

“I think a reminder for all of us is that every time you see a patient in clinic, it's a good idea to ensure that they have newer medications added or removed and reconcile them,” Jhaveri advised. This is particularly important for older patients or those with comorbidities who may be taking other medications that carry a risk for QT prolongation. Nursing teams should ensure a baseline ECG is performed and work closely with pharmacists or cardiologists if interactions are suspected.

The frontline of patient access

While the FDA approval is a major step forward, there is often a “lag time” of a few weeks to a couple of months before the drug is physically available in specialty pharmacies, as Jhaveri noted. Nurses should prepare patients for this potential delay and continue to provide education on what to expect once the first cycle begins.

By focusing on proactive education, diligent medication reconciliation, and open communication, oncology nurses can help patients successfully transition to this first-in-class therapy, ensuring they receive the full benefit of this new advance in precision medicine.