Commentary

Video

Dr Bardia on the Continued Investigation of Elacestrant in ER+/HER2– Breast Cancer

Aditya Bardia, MD, MPH, discusses the continued investigation of oral selective estrogen receptor degraders in patients with estrogen receptor-positive, HER2-negative metastatic breast cancer.

Aditya Bardia, MD, MPH, attending physician, medical oncology, Massachusetts General Hospital; associate professor, medicine, Harvard Medical School, discusses the continued investigation of oral selective estrogen receptor degraders (SERDs) in patients with estrogen receptor (ER)–positive, HER2-negative metastatic breast cancer.

Several ongoing clinical trials are focused on oral SERDs, which can be categorized into 3 groups, Bardia begins. The first category pertains to elacestrant (Orserdu), an FDA-approved agent, he states. This oral SERD was approved by the regulatory agency in January of 2023 for the treatment of postmenopausal women or adult men with ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer with disease progression following at least 1 line of endocrine therapy. This approval was supported by the phase 3 EMERALD trial (NCT03778931). Furthermore, the phase 1/2 ELEVATE trial (NCT05563220) is investigating elacestrant in combination with other agents, such as PI3K inhibitors and CDK4/6 inhibitors, in patients with metastatic breast cancer, Bardia explains. Notably, the second category of oral SERD clinical trials involves first-line studies comparing combinations of oral SERDs and CDK4/6 inhibitors with combinations of aromatase inhibitors (AIs) and CDK4/6 inhibitors, he adds

Furthermore, the third category includes trials examining circulating tumor DNA (ctDNA), where therapy may be altered based on elevated ctDNA levels, Bardia continues. An example is the phase 3 SERENA-6 trial (NCT04964934), a hybrid second-line study using ctDNA as a marker for switching therapy from an AI to camizestrant (AZD9833) in patients with ESR1-mutant, hormone receptor–positive, HER2-negative metastatic breast cancer, he explains. Positive data from this trial could influence the utilization of ctDNA and genotyping in breast cancer.

Resistance to conventional endocrine therapies, such as tamoxifen, AIs, and fulvestrant(Faslodex), often occurs because of mutations in the ER, which render the tumor estrogen independent, Bardia continues. Although drugs directly targeting ERs are often effective in these cases, conventional doses of fulvestrant and tamoxifen are not potent ER blockers in the presence of ESR1 mutations, he emphasizes. Novel agents, however, can degrade ERs and have demonstrated superior activity compared with fulvestrant and AIs in this scenario, Bardia says. Additionally, the appeal of these oral agents lies in their convenience for patients compared with intramuscular fulvestrant injections, he concludes.

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