Imlunestrant，一种口服选择性雌激素受体降解剂，作为单一疗法及与阿贝西利联合使用，用于复发性/晚期雌激素受体阳性子宫内膜样子宫内膜癌：1a/1b期EMBER研究结果
Imlunestrant, an oral selective estrogen receptor degrader, as monotherapy and combined with abemaciclib, in recurrent/advanced ER-positive endometrioid endometrial cancer: Results from the phase 1a/1b EMBER study.
作者信息
Yonemori Kan, Boni Valentina, Min Kim Gun, Meniawy Tarek M, Lombard Janine, Kaufman Peter A, Richardson Debra L, Bender Laura, Okera Meena, Matsumoto Koji, Giridhar Karthik V, García-Sáenz José Angel, Prenen Hans, de Speville Uribe Bernard Doger, Dizon Don S, Garcia-Corbacho Javier, Van Nieuwenhuysen Els, Li Yujia, Estrem Shawn T, Nguyen Bastien, Bacchion Francesca, Ismail-Khan Roohi, Jhaveri Komal, Banda Kalyan
机构信息
Department of Medical Oncology, National Cancer Center Hospital, Tokyo, Japan.
START Madrid-CIOCC, Quironsalud Madrid University Hospital, Madrid, Spain.
出版信息
Gynecol Oncol. 2024 Dec;191:172-181. doi: 10.1016/j.ygyno.2024.10.006. Epub 2024 Oct 22.
OBJECTIVE
Imlunestrant is a next-generation oral selective estrogen receptor degrader designed to deliver continuous estrogen receptor (ER) target inhibition. EMBER is a phase 1a/b trial of imlunestrant, as monotherapy and combined with targeted therapy, in patients with ER+ advanced breast cancer or endometrioid endometrial cancer (EEC). This report focuses on patients with ER+ EEC.
METHODS
EMBER used an i3 + 3 dose-escalation design to determine the recommended phase 2 dose (RP2D) followed by dose-expansion cohorts (1:1 randomization): imlunestrant monotherapy and imlunestrant plus abemaciclib (150 mg twice daily). Eligible patients had measurable disease and progression or recurrence after platinum-containing chemotherapy. Prior fulvestrant or aromatase inhibitor was not allowed. Secondary endpoints included safety, pharmacokinetics and antitumor activity.
RESULTS
In total, 72 patients with a median of 2 prior anticancer therapies were treated. Among the 39 patients who received imlunestrant (400 mg [RP2D], n = 33; 800 mg, n = 6), the most common treatment-emergent adverse events (TEAEs) were grade 1-2 nausea (35.9 %), diarrhea (25.6 %), urinary tract infection (25.6 %), and abdominal pain (20.5 %). Overall response rate (ORR) was 10.3 %, clinical benefit rate (CBR) was 33.3 %, and median progression-free survival (mPFS) was 3.8 months (95 % CI, 1.8-6.7). Among the 33 patients who received imlunestrant (400 mg [RP2D], n = 29; 800 mg, n = 4) plus abemaciclib, the most common TEAEs were diarrhea (87.9 %), nausea (66.7 %), fatigue (48.5 %), and anemia (45.5 %). ORR was 18.2 %, CBR was 42.4 %, and mPFS was 6.8 months (95 % CI, 2.1-12).
CONCLUSION
Imlunestrant, as monotherapy and combined with abemaciclib, has a manageable safety profile with preliminary evidence of antitumor activity in patients with ER+ EEC.
目的
Imlunestrant是一种新一代口服选择性雌激素受体降解剂，旨在持续抑制雌激素受体（ER）靶点。EMBER是一项1a/b期试验，研究Imlunestrant作为单药疗法以及与靶向治疗联合应用于雌激素受体阳性（ER+）晚期乳腺癌或子宫内膜样子宫内膜癌（EEC）患者的情况。本报告重点关注ER+ EEC患者。
方法
EMBER采用i3 + 3剂量递增设计来确定推荐的2期剂量（RP2D），随后是剂量扩展队列（1:1随机分组）：Imlunestrant单药疗法以及Imlunestrant加阿贝西利（每日两次，每次150 mg）。符合条件的患者在含铂化疗后有可测量的疾病且出现进展或复发。既往不允许使用氟维司群或芳香化酶抑制剂。次要终点包括安全性、药代动力学和抗肿瘤活性。
结果
总共治疗了72例患者，这些患者既往接受抗癌治疗的中位数为2次。在接受Imlunestrant治疗的39例患者中（400 mg [RP2D]，n = 33；800 mg，n = 6），最常见的治疗中出现的不良事件（TEAE）为1 - 2级恶心（35.9%）、腹泻（25.6%）、尿路感染（25.6%）和腹痛（20.5%）。总缓解率（ORR）为10.3%，临床获益率（CBR）为33.3%，中位无进展生存期（mPFS）为3.8个月（95% CI，1.8 - 6.7）。在接受Imlunestrant（400 mg [RP2D]，n = 29；800 mg，n = 4）加阿贝西利治疗的33例患者中，最常见的TEAE为腹泻（87.9%）、恶心（66.7%）、疲劳（48.5%）和贫血（45.5%）。ORR为18.2%，CBR为42.4%，mPFS为6.8个月（95% CI，2.1 - 12）。
结论
Imlunestrant作为单药疗法以及与阿贝西利联合应用时，具有可控的安全性，并有初步证据表明其对ER+ EEC患者具有抗肿瘤活性。
Zotero 插件