AMEERA-5：一项关于阿美司特联合哌柏西利与来曲唑联合哌柏西利用于既往未接受过治疗的雌激素受体阳性/人表皮生长因子受体2阴性晚期乳腺癌的随机、双盲3期研究。
AMEERA-5: a randomized, double-blind phase 3 study of amcenestrant plus palbociclib letrozole plus palbociclib for previously untreated ER+/HER2- advanced breast cancer.
作者信息
Bardia Aditya, Cortes Javier, Hurvitz Sara A, Delaloge Suzette, Iwata Hiroji, Shao Zhi-Ming, Kanagavel Dheepak, Cohen Patrick, Liu Qianying, Cartot-Cotton Sylvaine, Pelekanou Vasiliki, O'Shaughnessy Joyce
机构信息
Oncology/Hematology, Massachusetts General Hospital, Harvard Medical School, BHX-237, 55 Fruit Street, Boston, MA 02114, USA.
Oncology Department, International Breast Cancer Center (IBCC), Barcelona, Spain.
出版信息
Ther Adv Med Oncol. 2022 Mar 15;14:17588359221083956. doi: 10.1177/17588359221083956. eCollection 2022.
BACKGROUND
For estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC), the current standard first-line treatment includes an aromatase inhibitor in combination with a cyclin-dependent kinase 4/6 inhibitor. When resistance occurs, often related to the occurrence of mutations, selective estrogen receptor modulators or degraders (SERDs) may be used, alone or in combination regimens. Amcenestrant (SAR439859), an optimized oral SERD, has shown clinical antitumor activity in combination with palbociclib in patients with ER+/HER2- ABC and, as monotherapy, in patients with and without mutations. Here, we describe the study design of AMEERA-5, an ongoing, prospective, phase 3, randomized, double-blind, multinational study comparing the efficacy and safety of amcenestrant plus palbociclib letrozole plus palbociclib in patients with advanced (locoregional recurrent or metastatic) ER+/HER2- breast cancer.
METHODS
Patients are pre-/postmenopausal women and men with no prior systemic therapy for ABC. The planned enrollment is 1066 patients. Patients are randomized 1:1 to either amcenestrant 200 mg plus palbociclib 125 mg or letrozole 2.5 mg plus palbociclib 125 mg. Amcenestrant, letrozole, and their matching placebos are taken once daily continuously; palbociclib is taken once daily for 21 days, followed by 7 days off-treatment for a 28-day cycle. Treatment continues until disease progression, unacceptable toxicity, or decision to stop treatment. Pre-/perimenopausal women and men receive goserelin subcutaneously. Randomization is stratified by metastatic disease, menopausal status, and visceral metastases. The primary endpoint is progression-free survival. The key secondary endpoint is overall survival; others are safety, pharmacokinetics, and quality of life.
CONCLUSIONS
AMEERA-5 is evaluating the efficacy and safety of amcenestrant in combination with palbociclib as first-line therapy in pre-/postmenopausal women and men with ER+/HER2- ABC.
CLINICALTRIALS IDENTIFIER
NCT04478266.
背景
对于雌激素受体阳性（ER+）/人表皮生长因子受体2阴性（HER2-）的晚期乳腺癌（ABC），目前的标准一线治疗包括芳香化酶抑制剂联合细胞周期蛋白依赖性激酶4/6抑制剂。当出现耐药时，通常与突变的发生有关，可单独或联合使用选择性雌激素受体调节剂或降解剂（SERD）。Amcenestrant（SAR439859）是一种优化的口服SERD，已显示出与哌柏西利联合用于ER+/HER2-ABC患者时具有临床抗肿瘤活性，并且作为单一疗法，在有或无突变的患者中均有活性。在此，我们描述了AMEERA-5的研究设计，这是一项正在进行的、前瞻性、3期、随机、双盲、多中心研究，比较amcenestrant联合哌柏西利与来曲唑联合哌柏西利在晚期（局部区域复发或转移）ER+/HER2-乳腺癌患者中的疗效和安全性。
方法
患者为未接受过ABC全身治疗的绝经前/后女性和男性。计划招募1066名患者。患者按1:1随机分为amcenestrant 200 mg联合哌柏西利125 mg或来曲唑2.5 mg联合哌柏西利125 mg。Amcenestrant、来曲唑及其匹配的安慰剂均每日一次连续服用；哌柏西利每日一次服用21天，随后停药7天，为一个28天的周期。治疗持续至疾病进展、出现不可接受的毒性或决定停止治疗。绝经前/围绝经期女性和男性皮下注射戈舍瑞林。随机分组按转移性疾病、绝经状态和内脏转移进行分层。主要终点是无进展生存期。关键次要终点是总生存期；其他终点包括安全性、药代动力学和生活质量。
结论
AMEERA-5正在评估amcenestrant联合哌柏西利作为一线治疗方案在绝经前/后女性和男性ER+/HER2-ABC患者中的疗效和安全性。
临床试验标识符
NCT04478266。
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