Japanese subgroup analysis of the phase 3 MONARCH 3 study of abemaciclib as initial therapy for patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer

Background This was a Japanese subpopulation analysis of MONARCH 3, a randomized, double-blind, placebo-controlled phase 3 study of abemaciclib plus nonsteroidal aromatase inhibitors (NSAIs) for initial therapy for advanced breast cancer (ABC). Methods Eligibility included postmenopausal women with hormone receptor-positive, human epidermal growth factor receptor 2-negative ABC who had no prior systemic therapy in the advanced disease setting. Patients ( N = 493) were randomized 2:1 to receive abemaciclib or placebo (150 mg) plus either 1 mg anastrozole or 2.5 mg letrozole (physician’s choice). The primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), pharmacokinetics (PK), safety, and health-related quality of life (HRQoL). Results In Japan, 53 patients were randomized (abemaciclib, n = 38; placebo, n = 15). At final PFS analysis (November 3, 2017), median PFS was 29.1 and 14.9 months in the abemaciclib and placebo groups, respectively (hazard ratio 0.537; 95% confidence interval 0.224 – 1.289). ORR in measurable disease was 62.1 and 50.0% in the abemaciclib and placebo groups, respectively. The Japanese PK profile was comparable to that of the overall population. Consistent with prior studies, the most frequent adverse events reported were diarrhea (abemaciclib: any grade, 94.7%; grade ≥ 3, 10.5%; placebo: any grade, 46.7%; grade ≥ 3, 0%) and neutropenia (abemaciclib: any grade, 68.4%; grade ≥ 3, 21.1%; placebo: any grade, 0%). HRQoL outcomes were generally similar between treatments except for the diarrhea score, which favored placebo. Conclusions Consistent with findings in the overall population, abemaciclib plus NSAI was an effective initial treatment in the Japanese subpopulation, with a manageable safety profile. Clinical trial registration NCT02246621; U.S. National Library of Medicine: https://clinicaltrials.gov/ct2/show/NCT02246621 .