阿贝西利联合非甾体芳香化酶抑制剂作为HR+/HER2-晚期乳腺癌的初始治疗:MONARCH 3研究的最终总生存结果解读  

Abemaciclib Plus a Nonsteroidal Aromatase Inhibitor as Initial Therapy for HR+/HER2-Advanced Breast Cancer:Interpretation of Final Overall Survival Results of MONARCH 3

作　　者：张舒洁 褚嘉栋 李晓林 曹文明 ZHANG Shujie;CHU Jiadong;LI Xiaolin;CAO Wenming(Zhejiang Chinese Medical University,Hangzhou 310053,China;Zhejiang Cancer Hospital,Hangzhou 310022,China)

机构地区：[1]浙江中医药大学,浙江杭州310053 [2]浙江省肿瘤医院,浙江杭州310022

出　　处：《肿瘤学杂志》2024年第8期707-714,共8页Journal of Chinese Oncology

摘　　要：MONARCH 3研究是一项随机、双盲、安慰剂对照的Ⅲ期研究,入组18岁以上、绝经后、局部晚期不可手术或转移性激素受体(hormone receptor,HR)阳性/人表皮生长因子受体2(human epidermal growth factor receptor 2,HER2)阴性(HR+/HER2-)乳腺癌,要求晚期阶段未接受过任何系统性治疗。概括地说,MONARCH 3研究入组人群针对的是内分泌敏感HR+/HER2-乳腺癌的晚期一线治疗。入组患者按2∶1比例随机接受阿贝西利联合非甾体芳香化酶抑制剂(non-steroidal aromatase inhibitor,NSAI)或安慰剂联合NSAI治疗,主要终点为研究者评估意向治疗(intention-to-treat,ITT)人群的无进展生存期(progression-free survival,PFS),次要终点为总生存期(overall survival,OS),无化疗生存期(chemotherapy-free survival,CFS)是探索性终点。共有493例女性患者按2∶1的比例随机接受阿贝西利联合NSAI(阿贝西利组,n=328)或安慰剂联合NSAI(安慰剂组,n=165)治疗。中位随访8.1年后,阿贝西利组发生了198例(60.4%)OS事件,安慰剂组发生了116例(70.3%)OS事件,阿贝西利组和安慰剂组的中位OS分别为66.8个月和53.7个月(HR=0.804,95%CI:0.637~1.015,P=0.0664)。在内脏转移的亚组分析中,阿贝西利组发生了113例(65.3%)OS事件,安慰剂组发生了65例(72.2%)OS事件,中位OS分别为63.7个月和48.8个月(HR=0.758,95%CI:0.558~1.030,P=0.0757)。在观察期间没有新的安全事件发生。最终OS未获得统计学意义,因此在HR+/HER2-晚期乳腺癌临床研究中实现OS的显著获益或许还面临挑战。MONARCH 3 is a randomized,double-blind,placebo-controlled phaseⅢstudy that enrolls women aged 18 years or older with postmenopausal,locally advanced,unresectable or metastatic hormone receptor positive/human epidermal growth factor receptor 2 negative(HR+/HER2-)breast cancer without prior systemic therapy in the advanced setting.In summary,the MONARCH 3 study enrolled population was an advanced first-line treatment for endocrine-sensitive HR+/HER2-breast cancer.The patients were randomized in a 2∶1 ratio to receive Abemaciclib plus non-steroidal aromatase inhibitor(NSAI)or placebo plus NSAI treatment,with the primary endpoint being the investigator-assessed intention-to-treat(ITT)population’s progression-free survival(PFS)and the secondary endpoint being overall survival(OS).Chemotherapy-free survival(CFS)was an exploratory endpoint.A total of 493 women were randomized in a 2∶1 ratio to receive Abemaciclib plus NSAI(Abemaciclib group,n=328)or placebo plus NSAI(placebo group,n=165).After a median follow-up of 8.1 years,there were 198 OS events(60.4%)in the Abemaciclib arm and 116(70.3%)in the placebo arm(HR=0.804,95%CI:0.637~1.015,P=0.0664).Median OS for Abemaciclib and placebo was 66.8 months and 53.7 months,respectively.In the subgroup with visceral disease,there were 113(65.3%)OS events in the Abemaciclib arm and 65(72.2%)in the placebo arm(HR=0.758,95%CI:0.558~1.030,P=0.0757).Median OS for Abemaciclib and placebo was 63.7 months and 48.8 months,respectively.No new safety signals were observed.Ultimately,OS did not achieve statistical significance,so achieving significant OS benefit in HR+/HER2-advanced breast cancer clinical trials may still face challenges.

关 键 词：总生存期 乳腺肿瘤 阿贝西利 激素受体 人表皮生长因子受体2 CDK4/6抑制剂 一线治疗 

分 类 号：R737.9[医药卫生—肿瘤]