Japanese subpopulation analysis of MONARCH 2: phase 3 study of abemaciclib plus fulvestrant for treatment of hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer that progressed on endocrine therapy

Kenichi Inoue,Joji Mori,Yasuo Miyoshi,Yoshinori Tanizawa,Norikazu Masuda,Jan-Stefan Van Der Walt,Antonio Llombart-Cussac,Hirofumi Mukai,Sachi Sakaguchi,Yoshinori Ito,Hiroji Iwata,Tsutomu Kawaguchi,Takahiro Nakayama,George W Sledge,Masakazu Toi,Masato Takahashi

doi:10.1007/s12282-021-01239-8

Abstract

BackgroundThis was a Japanese subpopulation analysis of MONARCH 2, a double-blind, randomized, placebo-controlled, phase 3 study of abemaciclib plus fulvestrant in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer (ABC).MethodsEligible women had progressed on (neo)adjuvant endocrine therapy (ET), ≤ 12 months from end of adjuvant ET, or on first-line ET for ABC, and had not received chemotherapy for ABC. Patients were randomized 2:1 to receive abemaciclib or placebo plus fulvestrant. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), pharmacokinetics (PK), health-related quality of life (HRQoL), and safety.ResultsIn Japan, 95 patients were randomized (abemaciclib, n = 64; placebo, n = 31). At final PFS analysis (February 14, 2017), median PFS was 21.2 and 14.3 months, respectively, in the abemaciclib and placebo groups (hazard ratio: 0.672; 95% confidence interval: 0.380–1.189). Abemaciclib had a higher objective response rate (37.5%) than placebo (12.9%). PK and safety profiles for Japanese patients were consistent with those of the overall population, without clinically meaningful differences across most HRQoL dimensions evaluated. The most frequent adverse events in the abemaciclib versus placebo groups were diarrhea (95.2 versus 25.8%), neutropenia (79.4 versus 0%), and leukopenia (66.7 versus 0%). At a second data cutoff (June 20, 2019), median OS was not reached with abemaciclib and 47.3 months with placebo (hazard ratio: 0.755; 95% confidence interval: 0.390–1.463).ConclusionsResults of the Japanese subpopulation were consistent with the improved clinical outcomes and manageable safety profile observed in the overall population.Clinical trial registrationNCT02107703; U.S. National Library of Medicine: https://clinicaltrials.gov/ct2/show/NCT02107703.

Highlights

Breast cancer is the second leading cause of cancer mortality in women globally [1]
Extended author information available on the last page of the article factor receptor 2-negative (HER2−) breast cancer are typically treated with endocrine therapy (ET), but intrinsic and acquired ET resistance are common issues in patients with advanced or metastatic breast cancer [2, 3].The cyclin D pathway is an important target for overcoming mechanisms of ET resistance [4]
The Japanese subpopulation was generally comparable to the overall MONARCH 2 population for most baseline characteristics, a lower proportion of patients in the Japanese subpopulation were post-menopausal (60.0%) compared with the overall population (82.4%; Table 1)

Summary

Introduction

Breast cancer is the second leading cause of cancer mortality in women globally [1]. Women diagnosed with hormone receptor-positive (HR+), human epidermal growthExtended author information available on the last page of the article factor receptor 2-negative (HER2−) breast cancer are typically treated with endocrine therapy (ET), but intrinsic and acquired ET resistance are common issues in patients with advanced or metastatic breast cancer [2, 3].The cyclin D pathway is an important target for overcoming mechanisms of ET resistance [4]. In the intent-to-treat (ITT) population, abemaciclib plus fulvestrant significantly extended both progression-free survival (PFS; median: 16.4 versus 9.3 months, hazard ratio [HR]: 0.553, 95% confidence interval [CI]: 0.449–0.681, p < 0.001) and overall survival (OS; median: 46.7 versus 37.3 months, HR: 0.757; 95% CI: 0.606–0.945; p = 0.01) compared with placebo plus fulvestrant [12, 13] This was a Japanese subpopulation analysis of MONARCH 2, a double-blind, randomized, placebo-controlled, phase 3 study of abemaciclib plus fulvestrant in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer (ABC). Clinical trial registration NCT02107703; U.S National Library of Medicine: https://clinicaltrials.gov/ct2/show/NCT02 107703

Methods

Results

Discussion

Conclusion