Abemaciclib + fulvestrant has failed to hit interim efficacy targets in MONARCH 2 trial for women with hormone-receptor-positive, human epidermal growth factor receptor 2-negative locally advanced or metastatic breast cancer.- Eli Lilly

Eli Lilly and Company announced that following a pre-planned interim analysis for MONARCH 2, an independent Data Monitoring Committee (DMC) provided the recommendation to continue the study without modification as the interim efficacy criteria were not met. The MONARCH 2, Phase III trial compares abemaciclib plus fulvestrant versus placebo with fulvestrant in women with hormone-receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) locally advanced or metastatic breast cancer. The Phase III, double-blind study, designed to evaluate the safety and efficacy of abemaciclib in combination with fulvestrant, was conducted across 142 sites worldwide. The intent-to-treat population of 669 patients was randomized to receive abemaciclib or placebo orally every 12 hours on a continuous dosing schedule, given in combination with fulvestrant at the approved dose and schedule, until disease progression. Patients enrolled in the study had experienced disease progression on or within 12 months of receiving endocrine treatment in the neoadjuvant or adjuvant setting or while receiving first-line endocrine therapy for metastatic disease. Patients who had received chemotherapy in the metastatic setting were not eligible for the study. The primary endpoint for MONARCH 2 is progression-free survival (PFS).

The trial will continue into the first half of 2017 and will include a final analysis of PFS, overall survival and safety data. Lilly will await further data and continue to work with the FDA to inform its submission plan for single-agent abemaciclib, based on the MONARCH 1 study.

The Phase II study evaluated the single-agent activity and safety of abemaciclib in patients with refractory metastatic breast cancer, whose disease had progressed following multiple prior treatments, including chemotherapy. Along with MONARCH 1 and MONARCH 2, Lilly currently has three additional MONARCH trials evaluating abemaciclib in breast cancer. MONARCH 3 is a Phase III trial of abemaciclib in combination with a nonsteroidal aromatase inhibitor in patients with HR+, HER2- locoregionally recurrent or metastatic breast cancer.

Comment: There are two Phase II MONARCH trials: neoMONARCH, which is evaluating abemaciclib in combination with a nonsteroidal aromatase inhibitor in the neoadjuvant setting, and monarcHER, which is evaluating abemaciclib plus trastuzumab (with or without fulvestrant) in women with HR+, HER2+ locally advanced or metastatic breast cancer.