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.
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.
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DOI：
10.1200/jco.22.00338
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发表时间：
2022-10-01
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预治疗雌激素受体（ER）阳性/人表皮生长因子受体2（HER 2）阴性的晚期乳腺癌患者预后不良。Elacestrant是一种新型的口服选择性ER降解剂，在早期研究中表现出活性。这项随机化、开放标签、III期试验入组了接受过1 - 2线内分泌治疗、需要接受细胞周期蛋白依赖性激酶4/6抑制剂预治疗和≤ 1次化疗的ER阳性/HER 2阴性晚期乳腺癌患者。患者被随机分配至依来司群400 mg每日一次口服组或标准治疗（SOC）内分泌单药治疗组。主要终点是所有患者和可检测到ESR 1突变的患者的无进展生存期（PFS）。患者被随机分配至依西司群组（n = 239）或SOC组（n = 238）。在47.8%的患者中检测到ESR 1突变，43.4%的患者既往接受过两种内分泌治疗。所有患者（风险比= 0.70; 95% CI，0.55 - 0.88; P = 0.002）和ESR 1突变患者（风险比= 0.55; 95% CI，0.39 - 0.77; P = 0.0005）的PFS均延长。与治疗相关的3/4级不良事件发生率分别为7.2%和3.1%。导致治疗中止的与治疗相关的不良事件发生率分别为3.4%和0.9%。任何级别的恶心发生率分别为35.0%和18.8%（3/4级，分别为2.5%和0.9%）。在一项针对ER阳性/HER 2阴性晚期乳腺癌患者的III期试验中，依西司群是首个口服选择性ER降解剂，在总体人群和ESR 1突变患者中均显示相对于SOC的PFS显著改善，且安全性可控。
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. 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. 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). 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.