A Novel Agent for Previously Treated Patients with ER+/HER2− Advanced Breast Cancer

An investigational PROTAC ER degrader improved progression-free survival compared with fulvestrant in patients with ESR1 mutations.

Numerous novel anti-estrogens are in development with activity against tumors that express ESR1 mutations, which occur under pressure of treatment and confer resistance to subsequent endocrine therapy. The selective estrogen receptor degrader (SERD) elacestrant is the only such agent FDA-approved for tumors with ESR1 mutations.

The industry-funded, phase 3 VERITAC-2 trial enrolled 624 adults with ER+/HER2− advanced or metastatic breast cancer (including 270 with ESR1 mutations) who had received one line of CDK 4/6 inhibitor plus endocrine therapy. Investigators randomized patients to receive the investigational proteolysis-targeting chimera (PROTAC) ER degrader vepdegestrant (200 mg orally once daily continuously) or fulvestrant (500 mg intr…

Reviewing Author

William J. Gradishar, MD

Disclosures

Consultant/Advisory BoardLilly; AstraZeneca; Gilead

Grant/Research SupportBreast Cancer Research Foundation

Editorial BoardsClinical Breast Cancer; Oncology; Annals of Surgery; Breast Cancer Research and Treatment

Leadership Positions in Professional SocietiesNational Comprehensive Cancer Network (Chair, Breast Cancer Panel); American Board of Internal Medicine (Medical Oncology Board)