Abemaciclib is a potent, oral small-molecule inhibitor of CDK4 and 6 administered on a continuous dosing schedule, with evidence of single-agent antitumor activity and an acceptable safety profile when combined with an aromatase inhibitor in patients (pts) with refractory HR+ metastatic BC.
This phase II study (NCT02441946) compared the biologic activity of neoadjuvant abemaciclib plus anastrozole (ANZ; combo), abemaciclib monotherapy, and ANZ monotherapy in women with untreated early-stage invasive BC. All pts were randomized (1:1:1) for the first 2 weeks and then received combo therapy during the subsequent 14 weeks. Abemaciclib was administered 150 mg orally (PO) every 12 hours, and ANZ was administered 1 mg PO daily. Loperamide was administered as primary prophylaxis with each abemaciclib dose. The primary objective was the change in tissue Ki67 from baseline to week 2. Additional objectives included safety; clinical, radiologic, and pathological response; and changes in proliferation-associated genes (PAGs).
At the pre-specified 9-month interim analysis, data were available for safety (173 pts), Ki67 (64 pts), and PAGs (51 pts). Reduction in Ki67 geometric mean percent change from baseline was significantly greater (one-sided P < 0.001) with combo (-93.5%; n = 23) and abemaciclib (-93.1%; n = 19) than ANZ therapy (-71.0%; n = 22). There were a greater number of Ki67 responders (pts with Ki67 1 post baseline assessment.
Abemaciclib therapies reduced Ki67 more than ANZ alone. No new safety concerns were identified and diarrhea was less frequent and severe due to loperamide prophylaxis.
Clinical trial identification
Legal entity responsible for the study
Eli Lilly and Company
Eli Lilly and Company
S. Hurvitz: Amgen, Bayer, Boehringer Ingelheim, Genentech, GSK, Lilly, Novartis, Pfizer, Roche, Biomarin, Merrimack, OBI Pharma, PUMA, Dignitana, Medivation. C-S. Huang: Lilly, Roche, Genentech, Amgen, Novartis, OBI, Boehringer Ingelheim, BioMarin, AstraZeneca, Pfizer, Abbvie. S. Barriga, J.M. Schilder: Employed by Eli Lilly and Co. T.M. Costigan: Employed by and owns stock in Eli Lilly and Co. C.W. Caldwell: Employed by Eli Lilly and Company and a stock shareholder in the company. M.F. Press: Other from Eli Lilly and Company, during the conduct of the study; personal fees and other from Cepheid, other from Pfizer, outside the submitted work. M. Martin: Novartis, Roche, Celgene, AstraZeneca. All other authors have declared no conflicts of interest.