阿贝西利联合非甾体芳香化酶抑制剂或氟维司群用于激素受体阳性/人表皮生长因子受体2阴性晚期乳腺癌女性患者：随机III期MONARCH plus试验的最终结果
Abemaciclib plus non-steroidal aromatase inhibitor or fulvestrant in women with HR+/HER2- advanced breast cancer: Final results of the randomized phase III MONARCH plus trial.
作者信息
Hu Xichun, Zhang Qingyuan, Sun Tao, Yin Yongmei, Li Huiping, Yan Min, Tong Zhongsheng, Li Man, Teng Yue'e, Oppermann Christina Pimentel, Kanakasetty Govind Babu, Portugal Ma Coccia, Yang Liu, Zhang Wanli, Jiang Zefei
机构信息
Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang 150081, China.
出版信息
Chin Med J (Engl). 2024 Oct 10. doi: 10.1097/CM9.0000000000003151.
BACKGROUND
In the interim analysis of MONARCH plus, adding abemaciclib to endocrine therapy (ET) improved progression-free survival (PFS) and objective response rate (ORR) in predominantly Chinese postmenopausal women with HR+/HER2- advanced breast cancer (ABC). This study presents the final pre-planned PFS analysis.
METHODS
In the phase III MONARCH plus study, postmenopausal women in China, India, Brazil, and South Africa with HR+/HER2- ABC without prior systemic therapy in an advanced setting (cohort A) or progression on prior ET (cohort B) were randomized (2:1) to abemaciclib (150 mg twice daily [BID]) or placebo plus: anastrozole (1.0 mg/day) or letrozole (2.5 mg/day) (cohort A) or fulvestrant (500 mg) (cohort B). The primary endpoint was PFS of cohort A. Secondary endpoints included cohort B PFS (key secondary endpoint), ORR, overall survival (OS), safety, and health-related quality of life (HRQoL).
RESULTS
In cohort A (abemaciclib: n = 207; placebo: n = 99), abemaciclib plus a non-steroidal aromatase inhibitor improved median PFS vs . placebo (28.27 months vs . 14.73 months, hazard ratio [HR]: 0.476; 95% confidence interval [95% CI]: 0.348-0.649). In cohort B (abemaciclib: n = 104; placebo: n = 53), abemaciclib plus fulvestrant improved median PFS vs . placebo (11.41 months vs . 5.59 months, HR: 0.480; 95% CI: 0.322-0.715). Abemaciclib numerically improved ORR. Although immature, a trend toward OS benefit with abemaciclib was observed (cohort A: HR: 0.893, 95% CI: 0.553-1.443; cohort B: HR: 0.512, 95% CI: 0.281-0.931). The most frequent grade ≥3 adverse events in the abemaciclib arms were neutropenia, leukopenia, anemia (both cohorts), and lymphocytopenia (cohort B). Abemaciclib did not cause clinically meaningful changes in patient-reported global health, functioning, or most symptoms vs . placebo.
CONCLUSIONS
Abemaciclib plus ET led to improvements in PFS and ORR, a manageable safety profile, and sustained HRQoL, providing clinical benefit without a high toxicity burden or reduced quality of life.
TRIAL REGISTRATION
ClinicalTrials.gov (NCT02763566).
背景
在MONARCH plus研究的中期分析中，对于主要为中国绝经后HR+/HER2-晚期乳腺癌（ABC）患者，在内分泌治疗（ET）基础上加用阿贝西利可改善无进展生存期（PFS）和客观缓解率（ORR）。本研究展示了预先计划的最终PFS分析结果。
方法
在III期MONARCH plus研究中，来自中国、印度、巴西和南非的绝经后HR+/HER2- ABC患者，未接受过晚期阶段的全身治疗（队列A）或既往ET治疗后病情进展（队列B），按2:1随机分组，分别接受阿贝西利（150 mg每日两次[BID]）或安慰剂加：阿那曲唑（1.0 mg/天）或来曲唑（2.5 mg/天）（队列A）或氟维司群（500 mg）（队列B）。主要终点是队列A的PFS。次要终点包括队列B的PFS（关键次要终点）、ORR、总生存期（OS）、安全性和健康相关生活质量（HRQoL）。
结果
在队列A（阿贝西利：n = 207；安慰剂：n = 99）中，阿贝西利联合非甾体芳香化酶抑制剂与安慰剂相比改善了中位PFS（28.27个月 vs. 14.73个月，风险比[HR]：0.476；95%置信区间[95%CI]：0.348 - 0.649）。在队列B（阿贝西利：n = 104；安慰剂：n = 53）中，阿贝西利联合氟维司群与安慰剂相比改善了中位PFS（11.41个月 vs. 5.59个月，HR：0.480；95%CI：0.322 - 0.715）。阿贝西利在数值上提高了ORR。虽然数据尚不成熟，但观察到阿贝西利有OS获益的趋势（队列A：HR：0.893，95%CI：0.553 - 1.443；队列B：HR：0.512，95%CI：0.281 - 0.931）。阿贝西利治疗组中最常见的≥3级不良事件是中性粒细胞减少、白细胞减少、贫血（两个队列）和淋巴细胞减少（队列B）。与安慰剂相比，阿贝西利在患者报告的整体健康、功能或大多数症状方面未引起具有临床意义的变化。
结论
阿贝西利联合ET可改善PFS和ORR，安全性可控，HRQoL持续良好，在不带来高毒性负担或降低生活质量的情况下提供了临床获益。
试验注册
ClinicalTrials.gov（NCT02763566）
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