Elacestrant 在 ER+/HER2- 转移性乳腺癌伴 ESR1 突变肿瘤中的应用：III 期 EMERALD 试验中根据内分泌治疗联合 CDK4/6 抑制剂治疗持续时间的亚组分析及临床亚组分析。
Elacestrant in ER+, HER2- Metastatic Breast Cancer with ESR1-Mutated Tumors: Subgroup Analyses from the Phase III EMERALD Trial by Prior Duration of Endocrine Therapy plus CDK4/6 Inhibitor and in Clinical Subgroups.
机构信息
University of California Los Angeles (UCLA) Health Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, California.
International Breast Cancer Center (IBCC), Pangaea Oncology, Quironsalud Group, Barcelona, Spain; and IOB Madrid, Hospital Beata Maria Ana, and Faculty of Biomedical and Health Sciences, Department of Medicine, Universidad Europea de Madrid, Madrid, Spain.
出版信息
Clin Cancer Res. 2024 Oct 1;30(19):4299-4309. doi: 10.1158/1078-0432.CCR-24-1073.
PURPOSE
Elacestrant significantly prolonged progression-free survival (PFS) with manageable safety versus standard-of-care (SOC) endocrine therapy (ET) in patients with estrogen receptor-positive (ER+), HER2- metastatic breast cancer and tumors harboring estrogen receptor 1 (ESR1) mutation following ET plus a cyclin-dependent kinase 4/6 inhibitor (ET+CDK4/6i). In patients with ESR1-mutated tumors, we evaluated the efficacy and safety of elacestrant versus SOC based on prior ET+CDK4/6i duration and in clinical subgroups with prior ET+CDK4/6i ≥12 months.
PATIENTS AND METHODS
EMERALD, an open-label phase III trial, randomly assigned patients with ER+, HER2- metastatic breast cancer who had received 1-2 prior lines of ET, mandatory CDK4/6i, and ≤1 chemotherapy to elacestrant (345 mg daily) or SOC (aromatase inhibitor or fulvestrant). PFS was assessed across subgroups in post hoc exploratory analyses without adjustment for multiple testing.
RESULTS
In patients with ESR1-mutated tumors and prior ET+CDK4/6i ≥12 months, the median PFS for elacestrant versus SOC was 8.6 versus 1.9 months (HR, 0.41; 95% confidence interval, 0.26-0.63). In this population, the median PFS (in months) for elacestrant versus SOC was 9.1 versus 1.9 (bone metastases), 7.3 versus 1.9 (liver and/or lung metastases), 9.0 versus 1.9 (<3 metastatic sites), 10.8 versus 1.8 (≥3 metastatic sites), 5.5 versus 1.9 (PIK3 catalytic subunit α mutation), 8.6 versus 1.9 (tumor protein p53 gene mutation), 9.0 versus 1.9 (HER2-low), 9.0 versus 1.9 (ESR1D538G-mutated tumors), and 9.0 versus 1.9 (ESR1Y537S/N-mutated tumors). Subgroup safety was consistent with the overall population.
CONCLUSIONS
The duration of prior ET+CDK4/6i ≥12 months in metastatic breast cancer was associated with a clinically meaningful improvement in PFS for elacestrant compared with SOC and was consistent across all subgroups evaluated in patients with ER+, HER2-, ESR1-mutated tumors.
目的
在接受过内分泌治疗（ET）加细胞周期蛋白依赖性激酶 4/6 抑制剂（ET+CDK4/6i）以及雌激素受体 1（ESR1）突变的雌激素受体阳性（ER+）、HER2-转移性乳腺癌患者中，与标准治疗（SOC）内分泌治疗相比，Elacestrant 显著延长了无进展生存期（PFS），安全性可控。在接受过 ESR1 突变肿瘤的患者中，我们根据先前 ET+CDK4/6i 的持续时间以及先前 ET+CDK4/6i 持续时间≥12 个月的临床亚组，评估了 Elacestrant 与 SOC 的疗效和安全性。
患者和方法
EMERALD 是一项开放标签的 III 期试验，随机分配了接受过 1-2 线 ET、强制性 CDK4/6i 和≤1 种化疗的 ER+、HER2-转移性乳腺癌患者，接受 Elacestrant（每日 345mg）或 SOC（芳香酶抑制剂或氟维司群）治疗。事后探索性分析在不进行多次检验校正的情况下，在亚组中评估 PFS。
结果
在 ESR1 突变肿瘤且先前 ET+CDK4/6i 持续时间≥12 个月的患者中，Elacestrant 与 SOC 的中位 PFS 分别为 8.6 个月和 1.9 个月（HR，0.41；95%置信区间，0.26-0.63）。在该人群中，Elacestrant 与 SOC 的中位 PFS（月）分别为 9.1 个月和 1.9 个月（骨转移）、7.3 个月和 1.9 个月（肝和/或肺转移）、9.0 个月和 1.9 个月（<3 个转移部位）、10.8 个月和 1.8 个月（≥3 个转移部位）、5.5 个月和 1.9 个月（PIK3 催化亚单位α突变）、8.6 个月和 1.9 个月（肿瘤蛋白 p53 基因突变）、9.0 个月和 1.9 个月（HER2-低表达）、9.0 个月和 1.9 个月（ESR1D538G 突变肿瘤）和 9.0 个月和 1.9 个月（ESR1Y537S/N 突变肿瘤）。亚组安全性与总体人群一致。
结论
转移性乳腺癌中先前 ET+CDK4/6i 的持续时间≥12 个月与 Elacestrant 相比 SOC 显著改善了 PFS，在接受过 ET+CDK4/6i 治疗且 ESR1 突变的 ER+、HER2-转移性乳腺癌患者的所有评估亚组中均一致。
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