Dr Anderson on Novel and Emerging Therapeutics in HR+ Breast Cancer

Karen S. Anderson, MD, PhD, medical oncologist, Mayo Clinic Comprehensive Cancer Center, discusses novel and emerging therapies, as well as potential future targets, for the treatment of patients with hormone receptor (HR)–positive breast cancer.

One novel therapy in this space is the oral selective estrogen receptor degrader (SERD)elacestrant (Orserdu), Anderson begins. In January 2023, the FDA granted approval to elacestrant for the treatment of postmenopausal women or adult men with estrogen receptor–positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer who progressed on one or more prior lines of endocrine therapy, Anderson reports.

The approval was supported by findings from the phase 3 EMERALD trial (NCT03778931). In this trial, patients who received elacestrant experienced improved progression-free survival vs those who received standard-of-care (SOC) endocrine monotherapy with either an aromatase inhibitor or fulvestrant (Faslodex). This approval is particularly significant, as elacestrant is the first oral SERD to be approved in breast cancer.

In addition to being evaluated in the context of ESR1 mutations, elasectrant has been compared directly with fulvestrant, Anderson continues. Additionally, there are some data showing increased response rates with elacestrant in patients who have ESR1 mutations, she adds.

As familiarity with this class of drugs increases, research will focus on identifying patients that have these ESR1 mutations, when patients acquire them, and when these mutations can be detected utilizing circulating tumor DNA at a given time point, Anderson says. There may also be interest in evaluating elacestrant in earlier lines, specifically the adjuvant setting, to target the emergence of ESR1 mutations, she notes.

Aside from oral SERDs, other emerging therapeutics in HR-positive breast cancer include agents targeting the AKT pathway, Anderson states. This pathway is known to be a highly active in breast cancer. These include agents targeting mTOR or PIK3CA, such as the currently approved PIK3CA-targeted agent alpelisib (Piqray), she says. Overall, new targets in breast cancer are always under investigation, Anderson concludes.