Dr Wisinski on Treatment Developments in HR+/HER2– Breast Cancer

Kari Wisinski, MD, Endowed Professor of Hematology and Oncology, chief, Division of Hematology, Medical Oncology, and Palliative Care, Department of Medicine, University of Wisconsin (UW) School of Medicine and Public Health; associate director, Clinical Research, co-lead, Breast Cancer Disease Oriented Team, UW Carbone Cancer Center, discusses the development of oral selective estrogen receptor degraders (SERDs) and targeted therapies for the treatment of patients with hormone receptor (HR)–positive, HER2-negative breast cancer.

HR-positive breast cancer is one of the most common breast cancer subtypes, Wisinski says. Although combinations of anti-estrogen therapies and CDK4/6 inhibitors have improved outcomes for patients with HR-positive, HER2-negative disease, patients who progress on CDK4/6 inhibitors in the metastatic setting require further HR-targeted treatment, Wisinski explains. Several novel agents have been approved by the FDA for patients with HR-positive, HER2-negative metastatic breast cancer, and others are under investigation, Wisinski notes.

The oral SERD elacestrant (Orserdu) received FDA approval in 2023 for the treatment of postmenopausal patients with estrogen receptor–positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer. This regulatory decision was supported by findings from the phase 3 EMERALD trial (NCT03778931), in which elacestrant improved progression-free survival (PFS) vs investigator’s choice of endocrine therapy in patients with ESR1-mutated disease.

The PI3K inhibitor alpelisib (Piqray) was approved by the FDA in 2019 in combination with fulvestrant (Faslodex) for the treatment of postmenopausal patients with HR-positive, HER2-negative, PIK3CA-mutated, advanced or metastatic breast cancer who have progressed on or after endocrine therapy.

Furthermore, in 2023, the combination of the AKT inhibitor capivasertib (Truqap) and fulvestrant was approved by the FDA for the treatment of patients with HR-positive, HER2-negative, locally advanced or metastatic PIK3CA- AKT1-, or PTEN-mutated breast cancer who have progressed on 1 or more endocrine-based regimen in the metastatic setting or experienced disease recurrence on or within 12 months of completing adjuvant therapy. This regulatory decision was based on findings from the phase 3 CAPItello-291 trial (NCT04305496), in which capivasertib plus fulvestrant generated a PFS benefit vs placebo in this patient population.