Key takeaways:
- The FDA approved vepdegestrant for patients with ER–positive, HER2–negative, ESR1-mutated advanced or metastatic breast cancer.
- A phase 3 trial showed median PFS improvements compared with fulvestrant.
The FDA has approved the first proteolysis-targeting chimera for any oncologic indication.
Vepdegestrant (Veppanu, Arvinas Operations) — a heterobifunctional protein degrader — received approval for adults with ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer, as detected by an FDA-authorized test, according to an FDA press release.
The FDA has approved the first proteolysis-targeting chimera for any oncologic indication.
The indication applies to patients with disease progression after endocrine therapy.
The agency based its decision on the randomized, phase 3 VERITAC-2 study, which showed a 43% risk reduction for disease progression with the agent, compared with fulvestrant.
“For patients living with ESR1 mutant, ER+/HER2 advanced breast cancer, there have been minimal second-line treatment options once standard therapies are no longer effective,” Erika Hamilton, MD, director of the breast cancer research program at Sarah Cannon Research Institute and a principal investigator of the VERITAC-2 trial, said in a manufacturer release. “The introduction of a new, targeted treatment is an encouraging development for this community and highlights meaningful innovation in the way this disease is treated. The approval of vepdegestrant gives clinicians another tool in the breast cancer treatment arsenal and brings renewed hope to individuals who need additional options.”
The FDA also approved Guardant360 CDx (Arvinas Operations), a diagnostic device used to identify patients with ESR1 mutations.
In VERITAC-2, researchers randomly assigned 624 patients with ER-positive, HER2–negative advanced or metastatic breast cancer to receive vepdegestrant or fulvestrant.
All patients in VERITAC-2 needed to have experienced disease progression after one or two lines of endocrine therapy.
Patients in the investigative cohort received oral vepdegestrant once daily. Patients in the control group received intramuscular fulvestrant on days 1 and 15 of the first cycle and then once monthly afterward.
Among 270 patients who had ESR1 tumor mutations, those in the vepdegestrant arm had significantly improved median PFS (5 months vs. 2.1 months; HR = 0.57; 95% CI, 0.42-0.77) and a higher objective response rate (19% vs. 4%).
Researchers noted OS data to be immature at time of PFS analysis.
The most common adverse reactions included decreased white blood cells, increased aspartate aminotransferase, musculoskeletal pain, fatigue, decreased hemoglobin, decreased neutrophils, increased alanine aminotransferase, increased alkaline phosphatase, nausea, decreased blood potassium, increased bilirubin, decreased appetite, prolonged QT interval on ECG, decreased platelets and constipation, according to the manufacturer’s release.
Vepdegestrant has a recommended dose of 200 mg to be taken orally once a day with food until unacceptable toxicity or disease progression.
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