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.

Bidard, Francois-Clement;Kaklamani, Virginia G;Neven, Patrick;Streich, Guillermo;Bardia, Aditya;et.al.
(2022) Journal of clinical oncology — Vol. 40, n° 28, p. 3246-3256 (2022)

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  • Bidard, Francois-Clement
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  • Kaklamani, Virginia Gorcid-logo
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  • Neven, Patrick
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  • Streich, Guillermo
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  • Taylor, Donatienneorcid-logoUCLouvain
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  • Bardia, Adityaorcid-logo
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Abstract
(en) PURPOSE: Patients with pretreated estrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer have poor prognosis. Elacestrant is a novel, oral selective ER degrader that demonstrated activity in early studies. METHODS: This randomized, open-label, phase III trial enrolled patients with ER-positive/HER2-negative advanced breast cancer who had one-two lines of endocrine therapy, required pretreatment with a cyclin-dependent kinase 4/6 inhibitor, and ≤ 1 chemotherapy. Patients were randomly assigned to elacestrant 400 mg orally once daily or standard-of-care (SOC) endocrine monotherapy. Primary end points were progression-free survival (PFS) by blinded independent central review in all patients and patients with detectable ESR1 mutations. RESULTS: Patients were randomly assigned to elacestrant (n = 239) or SOC (n = 238). ESR1 mutation was detected in 47.8% of patients, and 43.4% received two prior endocrine therapies. PFS was prolonged in all patients (hazard ratio = 0.70; 95% CI, 0.55 to 0.88; P = .002) and patients with ESR1 mutation (hazard ratio = 0.55; 95% CI, 0.39 to 0.77; P = .0005). Treatment-related grade 3/4 adverse events occurred in 7.2% receiving elacestrant and 3.1% receiving SOC. Treatment-related adverse events leading to treatment discontinuations were 3.4% in the elacestrant arm versus 0.9% in SOC. Nausea of any grade occurred in 35.0% receiving elacestrant and 18.8% receiving SOC (grade 3/4, 2.5% and 0.9%, respectively). CONCLUSION: Elacestrant is the first oral selective ER degrader demonstrating a significant PFS improvement versus SOC both in the overall population and in patients with ESR1 mutations with manageable safety in a phase III trial for patients with ER-positive/HER2-negative advanced breast cancer. TRIAL REGISTRATION: ClinicalTrials.gov NCT03778931.
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Bidard, F.-C., Kaklamani, V. G., Neven, P., Streich, G., Montero, A. J., Forget, F., Mouret-Reynier, M.-A., Sohn, J. H., Taylor, D., Harnden, K. K., Khong, H., Kocsis, J., Dalenc, F., Dillon, P. M., Babu, S., Waters, S., Deleu, I., García Sáenz, J. A., Bria, E., et al. (2022). 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. Journal of clinical oncology, 40(28), 3246-3256. https://doi.org/10.1200/JCO.22.00338 (Original work published 2022)