MONARCH 3: trend for improved overall survival with abemaciclib plus aromatase inhibitor in advanced breast cancer


An interim analysis of phase III data further supports the use of abemaciclib plus non-steroidal aromatase inhibitor in patients with HR+, HER2– advanced breast cancer

In a Late-Breaking Abstract presentation at ESMO Congress 2022, results from a pre-specified second interim analysis (IA2) of the phase III MONARCH 3 trial showed that the addition of abemaciclib to a non-steroidal aromatase inhibitor (NSAI) resulted in a 12.6-month increase in median overall survival (mOS) in patients with hormone receptor (HR)-positive, HER2-negative advanced breast cancer (LBA15).

Abemaciclib, a cyclin-dependent kinase 4 and 6 inhibitor, is approved in combination with an NSAI as initial therapy for post-menopausal patients with HR-positive, HER2-negative advanced breast cancer based on the significant improvement in progression-free survival – the primary endpoint – observed in the MONARCH 3 phase III trial (J Clin Oncol. 2017;35:3638–3646). OS is a key secondary endpoint in the study and a pre-specified IA2 was performed after ~252 events had occurred in the intent-to-treat (ITT) population, representing 80% of planned events for the final OS analysis.

ESMO Congress 2022, LBA15

Figure 1. A pre-specified second interim analysis (IA2) of MONARCH 3 revealed that overall survival was 12.6 months longer with abemaciclib-based therapy versus placebo (ESMO Congress 2022, LBA15)

MONARCH 3 is a randomised, double-blind trial conducted in 158 sites in 22 countries. Patients with HR-positive, HER2-negative recurrent breast cancer that was not amenable to surgical resection or radiotherapy with curative intent, or with metastatic disease were randomised 2:1 to receive an NSAI plus abemaciclib (n=328) or an NSAI plus placebo (n=165). At the time of IA2, the median follow-up was 5.8 years. In the ITT population, median OS was 67.1 months for abemaciclib plus NSAI compared with 54.5 months for placebo plus NSAI (hazard ratio [HR] 0.754; 95% confidence interval [CI] 0.584– 0.974; 2-sided p=0.0301). Similar findings were observed in the subgroup of patients with visceral disease (sVD, n=263) with median OS of 65.1 months for abemaciclib plus NSAI compared with 48.8 months for placebo plus NSAI (HR 0.708; 95% CI 0.508– 0.985; 2-sided p=0.0392). However, in both the ITT and sVD populations, the threshold for formal statistical significance was not met in the IA2 according to the pre-defined alpha spend procedure. Safety data were consistent with the known safety profile of abemaciclib. Follow-up for the patients enrolled in MONARCH 3 is ongoing and a final OS analysis is planned once at least 315 and 189 OS events have occurred in the ITT and sVD populations, respectively.  

Abstract presented:

Goetz M, et al. MONARCH 3: Interim overall survival results of abemaciclib plus a nonsteroidal aromatase inhibitor in patients with HR+, HER2- advanced breast cancer. ESMO Congress 2022, LBA15

Proffered Paper Session, 09.09.2022, h. 16:00 – 17:30, Brest Auditorium

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and you can only disable them by changing your browser preferences.