Paluch-Shimon Shani, Neven Patrick, Huober Jens, Cicin Irfan, Goetz Matthew P, Shimizu Chikako, Huang Chiun-Sheng, Lueck Hans Joachim, Beith Jane, Tokunaga Eriko, Contreras Jessica Reyes, de Sant'Ana Rosane Oliveira, Wei Ran, Shahir Ashwin, Nabinger Sarah C, Forrester Tammy, Johnston Stephen R D, Harbeck Nadia
Hadassah University Hospital & Faculty of Medicine Hebrew University, Jerusalem 91120, Israel.
Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg, Leuven, Belgium.
Ther Adv Med Oncol. 2023 Feb 3;15:17588359231151840. doi: 10.1177/17588359231151840. eCollection 2023.
Abemaciclib is the first and only cyclin-dependent kinases 4 and 6 inhibitor approved for adjuvant treatment of hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-), node-positive, and high-risk early breast cancer (EBC), with indications varying by geography. Premenopausal patients with HR+, HER2- tumors may have different tumor biology and treatment response compared to postmenopausal patients.
We describe the efficacy and safety of abemaciclib plus endocrine therapy (ET) for the large subgroup of premenopausal patients with HR+, HER2- EBC in monarchE.
Randomized patients (1:1) received adjuvant ET with or without abemaciclib for 2 years plus at least 3 additional years of ET as clinically indicated.
Patients were stratified by menopausal status (premenopausal postmenopausal) at diagnosis. Standard ET (tamoxifen or aromatase inhibitor) with or without gonadotropin-releasing hormone agonist was determined by physician's choice. Invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS) by menopausal status were assessed at data cutoff on 1 April 2021 (median follow-up of 27 months).
Among randomized patients, 2451 (43.5%) were premenopausal and 3181 (56.4%) were postmenopausal. The choice of ET for premenopausal patients varied considerably between countries. Treatment benefit was consistent across menopausal status, with a numerically greater effect size in premenopausal patients. For premenopausal patients, abemaciclib with ET resulted in a 42.2% and 40.3% reduction in the risk of developing IDFS and DRFS events, respectively. Absolute improvement at 3 years was 5.7% for IDFS and 4.4% for DRFS rates. Safety profile for premenopausal patients was consistent with the overall safety population.
Abemaciclib with ET demonstrated clinically meaningful treatment benefit for IDFS and DRFS ET alone regardless of menopausal status and first ET, with a numerically greater benefit in the premenopausal compared to the postmenopausal population. Safety data in premenopausal patients are consistent with the overall safety profile of abemaciclib.
阿贝西利是首个也是唯一获批用于激素受体阳性（HR+）、人表皮生长因子受体2阴性（HER2-）、淋巴结阳性及高危早期乳腺癌（EBC）辅助治疗的细胞周期蛋白依赖性激酶4和6抑制剂，其适应症因地域而异。与绝经后患者相比，HR+、HER2-肿瘤的绝经前患者可能具有不同的肿瘤生物学特性和治疗反应。
我们描述了阿贝西利联合内分泌治疗（ET）在monarchE研究中HR+、HER2-EBC绝经前患者这一大型亚组中的疗效和安全性。
随机分组患者（1:1）接受辅助ET，联合或不联合阿贝西利治疗2年，并根据临床指征至少再接受3年ET治疗。
患者在诊断时按绝经状态（绝经前、绝经后）分层。标准ET（他莫昔芬或芳香化酶抑制剂）联合或不联合促性腺激素释放激素激动剂由医生选择。在2021年4月1日数据截止时（中位随访27个月）评估绝经状态下的无侵袭性疾病生存期（IDFS）和无远处复发生存期（DRFS）。
在随机分组患者中，2451例（43.5%）为绝经前患者，3181例（56.4%）为绝经后患者。不同国家绝经前患者的ET选择差异很大。治疗获益在不同绝经状态下是一致的，在绝经前患者中效应量在数值上更大。对于绝经前患者，阿贝西利联合ET分别使发生IDFS和DRFS事件的风险降低42.2%和40.3%。3年时IDFS的绝对改善率为5.7%，DRFS率为4.4%。绝经前患者的安全性概况与总体安全人群一致。
阿贝西利联合ET在IDFS和DRFS方面显示出具有临床意义的治疗获益，无论绝经状态和初始ET如何，与单独使用ET相比，在绝经前人群中的获益在数值上更大。绝经前患者的安全性数据与阿贝西利的总体安全性概况一致。
