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

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

doi:10.1097/CM9.0000000000003151

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

Chin Med J (Engl). 2024 Oct 10. doi: 10.1097/CM9.0000000000003151. Online ahead of print.

Authors

Xichun Hu¹, Qingyuan Zhang², Tao Sun³, Yongmei Yin⁴, Huiping Li⁵, Min Yan⁶, Zhongsheng Tong⁷, Man Li⁸, Yue'e Teng⁹, Christina Pimentel Oppermann¹⁰, Govind Babu Kanakasetty¹¹, Ma Coccia Portugal¹², Liu Yang¹³, Wanli Zhang¹³, Zefei Jiang¹⁴

Affiliations

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.

PMID: 39385327
DOI: 10.1097/CM9.0000000000003151

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) (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).

Associated data

ClinicalTrials.gov/NCT02763566