New Study Reveals Vepdegestrant Extends Survival in Patients with Advanced ER+ Breast Cancer Featuring ESR1 Mutations

Recent findings presented at the American Society of Clinical Oncology (ASCO) annual meeting highlight the promising benefits of vepdegestrant, an oral proteolysis-targeting chimera (PROTAC) that degrades estrogen receptors, in treating advanced estrogen receptor-positive (ER+), human epidermal growth factor receptor 2 (HER2)-negative breast cancer. This study, published in the New England Journal of Medicine, indicates that vepdegestrant significantly prolongs progression-free survival (PFS) in patients harboring ESR1 mutations, a common resistance mechanism to endocrine therapy.

The phase 3, open-label, randomized trial included patients with ER+/HER2- advanced breast cancer who had previously been treated with a CDK4/6 inhibitor and endocrine therapy. Participants were assigned to receive either vepdegestrant at 200 mg daily or fulvestrant at 500 mg on specific days of the treatment cycle. Results showed that among patients with ESR1 mutations, median PFS was 5.0 months with vepdegestrant compared to 2.1 months with fulvestrant, demonstrating a hazard ratio of 0.58. For the entire cohort, median PFS was 3.8 months versus 3.6 months, respectively.

While vepdegestrant demonstrated improved efficacy in patients with ESR1 mutations, adverse events of grade 3 or higher were reported in 23.4% of the vepdegestrant group versus 17.6% in the fulvestrant group, with a small percentage discontinuing treatment due to side effects. The study authors note that further research is needed to evaluate the long-term safety and effectiveness of vepdegestrant.

Funded by Pfizer, which is developing vepdegestrant, this research marks a significant step forward in targeted breast cancer therapies, especially for patients with ESR1 mutations resistant to current treatments. The findings suggest that vepdegestrant could become a valuable option for enhancing survival outcomes in this patient subgroup.