Elacestrant Improves PFS in ESR1 mutated, ER+/HER2– Breast Cancer

Data from the phase 3 EMERALD trial (NCT03778931) indicated that elacestrant (Orserdu) appeared to yield significant PFS benefit vs standard-of-care endocrine therapy in estrogen receptor–positive/HER2-negative metastatic breast cancer, specifically in patients with ESR1–mutant breast cancer, according to Janice Lu, MD, PhD.¹

In an interview with CancerNetwork® at the 2023 San Antonio Breast Cancer Symposium (SABCS), Lu, a professor and director of Breast Medical Oncology at Northwestern University Lurie Comprehensive Cancer Center, specifically addressed the benefits of elacestrant in highly clinical and key biomarker subgroups. These results remained consistent regardless of TP53 or PIK3CA mutation status, she said.

Transcript:

This subgroup analysis evaluated the benefit of single agent elacestrant in the endocrine sensitive population who received a prior CDK 4/6 inhibitor with a duration of at least 12 months in [patients with] ESR1 mutated tumors [including] highly prevalent clinical and key biomarker subgroups. [The population] included those with metastases of the bone, liver, and/or lungs, with common coexisting mutations, such as PIK3CA or TP53. [Patients had] ER-positive breast cancer—which occurs in about 30% to 40% of patients—HER2-low expression—which occurs up to 65% of patients.

These results demonstrated an improvement in PFS favoring elacestrant compared with standard-of-care in ESR1–mutant tumors that were consistent across all subgroups; all the Kaplan Meier curves were well separated. It showed that PFS ranged from 7.3 to 9.1 months for elacestrant regardless of TP53 mutation or HER2-low expression, which was significantly longer than the standard-of-care arm, which was 1.9 months. Regarding the coexistence of ESR1–mutant and PIK3CA–mutant tumors, elacestrant demonstrated a PFS of 5.5 months. That's consistent with the data reported from the phase 2 BYLieve study (NCT03056755) in those patients who had PIK3CA mutation and ESR1 mutations, although that was a very small cohort in a separate study.

These results suggest that when ESR1 mutated tumors remain endocrine sensitive; the ER pathway could be the main driver of the disease. In conclusion, single-agent elacestrant enables endocrine therapy sequencing in second-line therapy before other targeted therapies or drug combinations, chemotherapy-based regimens, or antibody-drug conjugates.