Elacestrant Conveys Improved PFS in Patients with ER+/HER2− Metastatic Breast Cancer with Prior CDK4/6 Inhibitors

The phase-3 EMERALD trial enrolled patients with ER-positive/HER2-negative (ER+/HER2−) advanced breast cancer.¹ Disease progression must have occurred during or within 28 days after treatment with 1 or2 lines of endocrine therapy and progression on previous CDK4/6 inhibitor (CDK4/6i) treatment in combination with fulvestrant or an aromatase inhibitor.¹ Patients with advanced/metastatic cancer who had 1 chemotherapy treatment were allowed in the study.¹ The study participants were randomly assigned to receive elacestrant 400 mg orally once a day or standard-of-care endocrine monotherapy.¹ The study demonstrated that patients treated with elacestrant had a prolonged progression-free survival (PFS) with a manageable safety profile compared with standard-of-care endocrine monotherapy. Patients with ESR1 mutations who received elacestrant and ≥12 months of CKD4/6i had a median PFS of 8.61 months; those receiving standard of care had a median PFS of 1.91 months. A subgroup analysis was performed on patients who had the ESR-1 mutation and concomitant liver and/or lung metastases, PIK3CA mutations, TP53 mutations, and HER2-low expression.

The study included 478 patients, with 239 receiving elacestrant and 239 receiving standard of care. The ESR-1 mutation was found in 228 patients and 159 patients had received CDK4/6i ≥12 months prior. Analysis of the 159 patients receiving CDK4/6i found 61 patients had the TP53 mutation, 62 patients had PIK3CA mutations, 77 patients had HER2-low expression, and 113 patients had liver and/or lung metastases. For those patients with liver and/or lung mutations, the median PFS with elacestrant was 7.26 months and with standard of care it was 1.87 months. Patients with PIK3CA mutations who received elacestrant had a median PFS of 5.45 months while those who received standard of care had a median PFS of 1.94 months. Patients with the TP53 mutations receiving elacestrant had a median PFS of 8.61 months and those treated with standard of care had a median PFS of 1.87. Patients with HER2-low expression treated with elacestrant had a median PFS of 9.03 while those treated with standard of care had a median PFS of 1.87 months.

Source:

Bidard A, O’Shaughnessy J, Bidard F-C, et al. Elacestrant vs. standard of care in ER+/HER2- advanced or metastatic breast cancer (mBC) with ESR1 mutation: key biomarkers and clinical subgroup analyses from the phase-3 EMERALD trial. Poster presented at: San Antonio Breast Cancer Symposium. December 8, 2023; San Antonio, TX. Abstract # PS17-02.

Reference:

1. Bidard FC, Kaklamani VG, Neven P, et al. Elacestrant (oral selective estrogen receptor degrader) Versus Standard Endocrine Therapy for Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: Results From the Randomized Phase III EMERALD Trial [published correction appears in J Clin Oncol. 2023;41(23):3962]. J Clin Oncol. 2022;40:3246-3256.