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Higher response rates and delayed progression when adding abemaciclib to endocrine therapy in postmenopausal women with HR+/HER2- advanced breast cancer

Results of the MONARCH 3 trial showed that adding the cyclin-dependent kinase (CDK) 4/6 inhibitor abemaciclib to endocrine therapy improves the progression-free survival (PFS) compared to endocrine therapy alone in postmenopausal women with hormone receptor positive (HR+), HER2 negative (HER2-) advanced breast cancer. Also the objective response rate (ORR) was significantly higher when abemaciclib was added. As such, this is the third phase III trial demonstrating that the combination of endocrine therapy with a CDK4/6 inhibitor is better than endocrine therapy alone.

MONARCH 3 evaluates abemaciclib, an oral selective CDK4/6 inhibitor, plus the non-steroidal aromatase inhibitors (NSAI) anastrozole or letrozole as initial therapy for women with HR+/HER2- advanced breast cancer. The study included 493 endocrine naïve patients or patients with disease relapse >12 months after (neo)adjuvant endocrine therapy and randomized them (2:1) to receive abemaciclib (150mg, twice daily continuous schedule) or placebo, both in combination with anastrozole (1mg daily) or letrozole (2.5mg daily). The primary endpoint was PFS, while ORR was a key secondary objective.

Results of the interim analysis at 18 months showed that, compared to endocrine therapy alone, the combination of abemaciclib and endocrine therapy significantly prolonged the PFS with a hazard ratio (HR) of 0.543 (median PFS: not reached with abemaciclib versus 14.7 months in placebo arm; HR[95%CI]: 0.543[0.409-0.723]; p = 0.000021). In patients with measurable disease, the ORR was 59% in the abemaciclib arm versus 44% in the placebo arm (p= 0.004).

The most frequent adverse events seen with abemaciclib versus placebo were diarrhea (81.3% versus. 29.8%), neutropenia (41.3% versus 1.9%), and fatigue (40.1% versus 31.7%).

In summary, abemaciclib plus endocrine therapy demonstrated a tolerable safety profile and was an effective initial treatment for patients with HR+/HER2- advanced breast cancer, significantly improving PFS and ORR. As such, abemaciclib is the third CDK4/6 inhibitor to be tested in advanced breast cancer and the MONARCH 3 trial confirms the role of this new class of agents in combination with endocrine therapy in the treatment of metastatic breast cancer.


di Leo A, Toi M, Campone M, et al. MONARCH 3: Abemaciclib as initial therapy for patients with HR+/HER2- advanced breast cancer. Presented at ESMO 2017, abstract 3260O_PR.

Speaker Angelo Di Leo

di Leo

Prof. Angelo Di Leo, MD, Sandro Pitigliani Medical Oncology Department, Hospital of Prato, Instituto Toscano Tumori, Prato, Italy


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