Issues

Patnaik and colleagues report results of a first-in-human multicenter phase I dose-escalation trial to evaluate the safety and tolerability of abemaciclib, a small-molecule inhibitor of cyclin-dependent kinases (CDK) 4 and 6, in patients with advanced solid tumors. Abemaciclib was safe and well tolerated, with few serious adverse events, which allowed continuous dosing. Consistent with on-target inhibition of CDK4 and CDK6, which normally drive progression from G₁- to S-phase by phosphorylating the RB tumor suppressor protein, a decrease in phosphorylated RB in epidermal keratinocytes was correlated with clinical response. Single-agent treatment with abemaciclib led to disease control (partial responses or stable disease) in patients with a range of advanced solid tumors, including breast cancer, non–small cell lung cancer, glioblastoma, melanoma, and colorectal cancer, supporting further clinical development of this compound. For details, please see the article by Patnaik and colleagues 740.