口服选择性雌激素受体降解剂 Imlunestrant 作为单药或与阿柏西尼联合治疗复发性/晚期 ER 阳性子宫内膜样内膜癌：1a/1b期EMBER研究结果。

IF 4.5 2区医学 Q1 OBSTETRICS & GYNECOLOGY

Gynecologic oncology Pub Date : 2024-10-22 DOI:10.1016/j.ygyno.2024.10.006

Kan Yonemori , Valentina Boni , Kim Gun Min , Tarek M. Meniawy , Janine Lombard , Peter A. Kaufman , Debra L. Richardson , Laura Bender , Meena Okera , Koji Matsumoto , Karthik V. Giridhar , José Angel García-Sáenz , Hans Prenen , Bernard Doger de Speville Uribe , Don S. Dizon , Javier Garcia-Corbacho , Els Van Nieuwenhuysen , Yujia Li , Shawn T. Estrem , Bastien Nguyen , Kalyan Banda

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引用次数: 0

摘要

目的：依仑司群是一种新一代口服选择性雌激素受体降解剂，旨在提供持续的雌激素受体（ER）靶点抑制。EMBER是一项1a/b期试验，对ER+晚期乳腺癌或子宫内膜样内膜癌（EEC）患者进行伊莫司群单药或联合靶向治疗。本报告主要针对ER+ EEC患者：EMBER采用i3 + 3剂量递增设计来确定推荐的2期剂量（RP2D），然后进行剂量扩展队列（1:1随机化）：imlunestrant单药治疗和imlunestrant加abemaciclib（150毫克，每天两次）。符合条件的患者在接受含铂化疗后病情进展或复发。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：共有72名患者接受了治疗，其中中位数患者曾接受过2次抗癌治疗。在接受依仑司群（400 毫克 [RP2D]，n = 33；800 毫克，n = 6）治疗的 39 名患者中，最常见的治疗突发不良事件（TEAEs）为 1-2 级恶心（35.9%）、腹泻（25.6%）、尿路感染（25.6%）和腹痛（20.5%）。总体反应率（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）。在接受依仑司坦（400 毫克 [RP2D]，n = 29；800 毫克，n = 4）加阿培莫司利治疗的 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作为单药或与abemaciclib联合用药，在ER+ EEC患者中具有可控的安全性和初步的抗肿瘤活性。

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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

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.

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来源期刊

Gynecologic oncology 医学-妇产科学

CiteScore

8.60

自引率

6.40%

发文量

1062

审稿时长

37 days

期刊介绍： Gynecologic Oncology, an international journal, is devoted to the publication of clinical and investigative articles that concern tumors of the female reproductive tract. Investigations relating to the etiology, diagnosis, and treatment of female cancers, as well as research from any of the disciplines related to this field of interest, are published. Research Areas Include: • Cell and molecular biology • Chemotherapy • Cytology • Endocrinology • Epidemiology • Genetics • Gynecologic surgery • Immunology • Pathology • Radiotherapy