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.
10.1097/CM9.0000000000003151
- Author:
Xichun HU
1
;
Qingyuan ZHANG
2
;
Tao SUN
3
;
Yongmei YIN
4
;
Huiping LI
5
;
Min YAN
6
;
Zhongsheng TONG
7
;
Man LI
8
;
Yue'e TENG
9
;
Christina Pimentel OPPERMANN
10
;
Govind Babu KANAKASETTY
11
;
Ma Coccia PORTUGAL
12
;
Liu YANG
13
;
Wanli ZHANG
13
;
Zefei JIANG
14
Author Information
1. Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
2. Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang 150081, China.
3. Department of Medical Oncology, Cancer Hospital of China Medical University/Liaoning Cancer Hospital, Shenyang, Liaoning 110042, China.
4. Department of Oncology, Jiangsu Province Hospital, Nanjing, Jiangsu 210029, China.
5. Department of Breast Oncology, Peking University Cancer Hospital & Institute 100142, Beijing, China.
6. Department of Breast Disease, Henan Breast Cancer Center, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, Henan 450052, China.
7. Department of Breast Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China.
8. Department of Oncology, Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116023, China.
9. Department of Oncology, The First Hospital of China Medical University, Shenyang, Liaoning 110001, China.
10. Centro de Pesquisa Clínica de Oncologia e Hematologia, Hospital Mãe de Deus/AESC, Porto Alegre, Brazil.
11. Department of Medical Oncology, HCG Hospitals and Kidwai Memorial Institute of Oncology, Bangalore, India.
12. Clinical Trial Department, Eastleigh Breast Care Center, Pretoria, South Africa.
13. Eli Lilly and Company, Shanghai 200021, China.
14. Department of Breast Cancer, Fifth Medical Center of Chinese PLA General Hospital, Beijing 100071, China.
- Publication Type:Clinical Trial, Phase III
- Keywords:
Abemaciclib;
Advanced breast cancer;
Cyclin-dependent kinase 4/6 inhibitor;
MONARCH plus;
Progression-free survival
- MeSH:
Humans;
Female;
Fulvestrant/therapeutic use*;
Breast Neoplasms/metabolism*;
Aminopyridines/therapeutic use*;
Benzimidazoles/therapeutic use*;
Middle Aged;
Aromatase Inhibitors/therapeutic use*;
Aged;
Receptor, ErbB-2/metabolism*;
Adult;
Letrozole/therapeutic use*;
Antineoplastic Combined Chemotherapy Protocols/therapeutic use*;
Anastrozole/therapeutic use*
- From:
Chinese Medical Journal
2025;138(12):1477-1486
- CountryChina
- Language:English
-
Abstract:
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 on days 1 and 15 of cycle 1 and then on day 1 of each subsequent cycle) (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).
