US Food and Drug Administration Approval Summary: Elacestrant for Estrogen Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative, ESR1 -Mutated Advanced or Metastatic Breast Cancer

作者：Mirat Shah, Hima Lingam, Xin Gao, Haley Gittleman, Mallorie H. Fiero, Danielle Krol, Nikolett M. Biel, Tiffany K. Ricks, Wentao Fu, Salaheldin S. Hamed, Fang Li, Jillian Sun, Jianghong Fan, Robert N. Schuck, Manuela Grimstein, Liu-Ya Tang, Shyam Kalavar, Abde M. Abukhdeir, Anand Pathak, Soma Ghosh, Ilynn Bulatao, Amy Tilley, William F. Pierce, Bronwyn D. Mixter, Shenghui Tang, Richard Pazdur, Paul G. Kluetz, Laleh Amiri‐Kordestani · 发表于：Journal of Clinical Oncology · 年份：2024 · DOI：10.1200/jco.23.02112 · 被引用次数：48 · 研究领域：Advanced Breast Cancer Therapies、HER2/EGFR in Cancer Research、Cancer Treatment and Pharmacology

PURPOSE The US Food and Drug Administration (FDA) approved elacestrant for the treatment of postmenopausal women or adult men with estrogen receptor–positive (ER+), human epidermal growth factor receptor 2–negative (HER2–), estrogen receptor 1 ( ESR1)–mutated advanced or metastatic breast cancer with disease progression after at least one line of endocrine therapy (ET). PATIENTS AND METHODS Approval was based on EMERALD (Study RAD1901-308), a randomized, open-label, active-controlled, multicenter trial in 478 patients with ER+, HER2– advanced or metastatic breast cancer, including 228 patients with ESR1 mutations. Patients were randomly assigned (1:1) to receive either elacestrant 345 mg orally once daily (n = 239) or investigator's choice of ET (n = 239). RESULTS In the ESR1-mut subgroup, EMERALD demonstrated a statistically significant improvement in progression-free survival (PFS) by blinded independent central review assessment (n = 228; hazard ratio [HR], 0.55 [95% CI, 0.39 to 0.77]; P value = .0005). Although the overall survival (OS) end point was not met, there was no trend toward a potential OS detriment (HR, 0.90 [95% CI, 0.63 to 1.30]) in the ESR1-mut subgroup. PFS also reached statistical significance in the intention-to-treat population (ITT, N = 478; HR, 0.70 [95% CI, 0.55 to 0.88]; P value = .0018). However, improvement in PFS in the ITT population was primarily attributed to results from patients in the ESR1-mut subgroup. More patients who received elacestrant...