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, 

-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 

 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 

As familiarity with this class of drugs increases, research will focus on identifying patients that have these 

 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 

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.

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Karen S. Anderson, MD, PhD, discusses novel and emerging therapies, as well as potential future targets, for the treatment of patients with hormone receptor–positive breast cancer.


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

Karen S. Anderson, MD, PhD, medical oncologist, Mayo Clinic Comprehensive Cancer Center, discusses the evolution of antibody-drug conjugates (ADCs) in the treatment of different subgroups of patients with metastatic breast cancer.

Sacituzumab govitecan-hziy (Trodelvy) has a well-established role in the second- and third-line treatment of patients with metastatic triple-negative breast cancer, Anderson says. Additionally, in February 2023, 

 for the treatment of adult patients with unresectable locally advanced or metastatic hormone receptor (HR)–positive, HER2-negative breast cancer who have received endocrine-based therapy and at least 2 additional systemic therapies in the metastatic setting.

Fam-trastuzumab deruxtecan-nxki (Enhertu) displayed benefits for patients with metastatic HER2-low breast cancer who had HR-positive or -negative tumors in the phase 3 DESTINY-Breast04 (NCT03734029) trial. Trastuzumab deruxtecan is now approved by the FDA for the treatment of select patients with HER2-positive breast cancer after previously receiving approval in the HER2-positive space. With the efficacy displayed by the ADC in patients with HER2-low disease, additional work is being conducted to improve the detection of HER2-low tumors, Anderson notes, adding that HER2-low could potentially represent half of this patient population. However, HER2-low remains difficult to measure due to variability in the testing, Anderson notes.

Since trastuzumab deruxtecan and sacituzumab govitecan are both potentially options for some patients with metastatic breast cancer, determining how to sequence these ADCs remains an important task, Anderson continues. Other investigations are examining novel ADCs and emerging targets, Anderson adds.

With the ADCS that have already been approved and the other agents coming down the pipeline, their continued emergence could move the use of chemotherapy further down the list in terms of prioritization of therapeutic approaches, Anderson concludes.

Karen S. Anderson, MD, PhD, discusses the evolution of antibody-drug conjugates in the treatment of different subgroups of patients with metastatic breast cancer.


Karen S. Anderson, MD, PhD

Articles

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

Dr Anderson on the Evolution of ADCs in Metastatic Breast Cancer