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
Department of Medical Oncology, National Cancer Center Hospital, Tokyo, Japan.
START Madrid-CIOCC, Quironsalud Madrid University Hospital, Madrid, Spain.
Gynecol Oncol. 2024 Dec;191:172-181. doi: 10.1016/j.ygyno.2024.10.006. Epub 2024 Oct 22.
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.
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.
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).
Imlunestrant, as monotherapy and combined with abemaciclib, has a manageable safety profile with preliminary evidence of antitumor activity in patients with ER+ EEC.
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。
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。
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）。
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。
