Potent cell cycle inhibition and upregulation of immune response with abemaciclib and anastrozole in neoMONARCH, Phase 2 neoadjuvant study in HR+/HER2- breast cancer

Purpose: neoMONARCH assessed the biological effects of abemaciclib in combination with anastrozole in the neoadjuvant setting. Experimental Design: Postmenopausal women with stage I-IIIB HR+/HER2-   breast cancer were randomized to a 2-week lead-in of abemaciclib, anastrozole, or abemaciclib plus anastrozole followed by 14 weeks of the combination. The primary objective evaluated change in Ki67 from baseline to 2 weeks of treatment. Additional objectives included clinical, radiologic, and pathologic responses, safety, as well as gene expression changes related to cell proliferation and immune response. Results: Abemaciclib, alone or in combination with anastrozole, achieved a significant decrease in Ki67 expression and led to potent cell cycle arrest after 2 weeks of treatment compared to anastrozole alone. More patients in the abemaciclib-containing arms versus anastrozole alone achieved complete cell cycle arrest (58%/68% vs 14%, P