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

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...

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Main Authors: Xichun Hu, Qingyuan Zhang, Tao Sun, Yongmei Yin, Huiping Li, Min Yan, Zhongsheng Tong, Man Li, Yue’e Teng, Christina Pimentel Oppermann, Govind Babu Kanakasetty, MA Coccia Portugal, Liu Yang, Wanli Zhang, Zefei Jiang, Sihan Zhou, Xiuyuan Hao
Format: Article
Language:English
Published: Wolters Kluwer 2025-06-01
Series:Chinese Medical Journal
Online Access:http://journals.lww.com/10.1097/CM9.0000000000003151
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Summary: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).
ISSN:0366-6999
2542-5641