MONARCH plus: abemaciclib plus endocrine therapy in women with HR+/HER2- advanced breast cancer: the multinational randomized phase III study
Qing Yuan Zhang, Tao Sun, Yong Mei Yin, Hui Ping Li, Min Yan, Zhong Sheng Tong, Christina P Oppermann, Yun Peng Liu, Romulo Costa, Man Li, Ying Cheng, Qu Chang Ouyang, Xi Chen, Ning Liao, Xin Hong Wu, Xiao Jia Wang, Ji Feng Feng, Roberto Hegg, G B Kanakasetty, Maria A Coccia-Portugal, Ru Bing Han, Yi Lu, Hai Dong Chi, Ze Fei Jiang, Xi Chun Hu, Qing Yuan Zhang, Tao Sun, Yong Mei Yin, Hui Ping Li, Min Yan, Zhong Sheng Tong, Christina P Oppermann, Yun Peng Liu, Romulo Costa, Man Li, Ying Cheng, Qu Chang Ouyang, Xi Chen, Ning Liao, Xin Hong Wu, Xiao Jia Wang, Ji Feng Feng, Roberto Hegg, G B Kanakasetty, Maria A Coccia-Portugal, Ru Bing Han, Yi Lu, Hai Dong Chi, Ze Fei Jiang, Xi Chun Hu
Abstract
Aim: To compare the efficacy, safety, and tolerability of abemaciclib plus endocrine therapy (ET) versus ET alone in postmenopausal women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (ABC) from China, Brazil, India, and South Africa.
Methods: This randomized, double-blind, phase III study was conducted between 9 December 2016 and 29 March 2019. Postmenopausal women with HR-positive, HER2-negative ABC with no prior systemic therapy in an advanced setting (cohort A) or progression on prior ET (cohort B) received abemaciclib (150 mg twice daily) or placebo plus: anastrozole (1 mg/day) or letrozole (2.5 mg/day) (cohort A) or fulvestrant (500 mg per label) (cohort B). The primary endpoint was progression-free survival (PFS) in cohort A, analyzed using the stratified log-rank test. Secondary endpoints were PFS in cohort B (key secondary endpoint), objective response rate (ORR), and safety. This interim analysis was planned after 119 PFS events in cohort A.
Results: In cohort A, 207 patients were randomly assigned to the abemaciclib arm and 99 to the placebo arm. Abemaciclib significantly improved PFS versus placebo (median: not reached versus 14.7 months; hazard ratio 0.499; 95% confidence intervals (CI) 0.346-0.719; p = 0.0001). ORR was 65.9% in the abemaciclib arm and 36.1% in the placebo arm (p < 0.0001, measurable disease population). In cohort B, 104 patients were randomly assigned to the abemaciclib arm and 53 to the placebo arm. Abemaciclib significantly improved PFS versus placebo (median: 11.5 versus 5.6 months; hazard ratio 0.376; 95% CI 0.240-0.588; p < 0.0001). ORR was 50.0% in the abemaciclib arm and 10.5% in the placebo arm (p < 0.0001, measurable disease population). The most frequent grade ⩾3 adverse events in the abemaciclib arms were neutropenia, leukopenia, and anemia (both cohorts), and lymphocytopenia (cohort B).
Conclusion: The addition of abemaciclib to ET demonstrated significant and clinically meaningful improvement in PFS and ORR, without new safety signals observed in this population.Trial Registration: ClinicalTrials.gov identifier: NCT02763566.
Keywords: abemaciclib; aromatase inhibitors; breast neoplasms; cyclin-dependent kinase 4; cyclin-dependent kinase 6; fulvestrant.
Conflict of interest statement
Conflict of interest: RBH, YL and HDC are employees and minor shareholders of Eli Lilly and Company. XHW has received research funding from Eli Lilly and Company. QYZ, TS, YMY, HPL, MY, ZST, CPO, YPL, RC, ML, YC, QCO, XC, NL, XJW, JFF, RH, GBK, MAC-P, ZJ and XCH have no conflicts of interest to declare.
© The Author(s), 2020.
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Source: PubMed