Dr. Hamilton on the Potential Integration of Novel SERDs in ER+/HER2- Breast Cancer

Erika P. Hamilton, MD, director, Breast Cancer and Gynecologic Cancer Research Program, principal investigator Sarah Cannon Research Institute, discusses the potential integration of novel selective estrogen receptor (ER) degraders (SERDs) into the armamentarium for ER-positive, HER2-negative breast cancer.

Oral SERDs represent a promising class of agents under clinical investigation for use in ER-positive, HER2-negative breast cancer, Hamilton says. With more than 10 agents in development, these agents could have utility in multiple settings.

The most logical place in which to use these agents is the second-line setting in replacement of fulvestrant (Faslodex), Hamilton explains. The results of the phase 2 VERONICA trial (NCT03584009) failed to demonstrate an improvement in clinical benefit rate or progression-free survival with the combination of venetoclax (Venclexta) plus fulvestrant vs fulvestrant alone in patients with locally advanced or metastatic ER-positive, HER2-negative breast cancer who had progressed on a CDK4/6 inhibitor, which are now standard first-line therapies. Moreover, the results showed modest activity with single-agent fulvestrant, underscoring a need for improved agents in this setting, Hamilton says.

As such, emerging phase 1 data with these agents appear encouraging and suggest novel SERDs could improve upon the efficacy of single-agent fulvestrant in the second-line setting, Hamilton concludes.