Palbociclib exposure-response analyses in second-line treatment of hormone-receptor positive advanced breast cancer (ABC).

1053Background: Palbociclib (PAL) is an oral inhibitor of cyclin-dependent kinases 4 and 6 approved for ABC. Exposure-response analyses for efficacy and safety endpoints were performed to evaluate the current PAL clinical dosing regimen (125 mg daily, 3 weeks on and 1 week off) and dose modification strategy in 2nd-line ABC. Methods: The present analyses used data from PALOMA3, a phase 3 study comparing the safety and efficacy of fulvestrant plus either PAL or placebo in 2nd-line ABC patients (PTs). A Bayesian pharmacokinetic (PK) analysis was conducted to estimate PAL PK parameters for individual PTs. Average concentration of PAL over the entire treatment (Cavg) was derived from average daily dose intensity divided by post hoc estimates of clearance for each PT. Time varying Cavg (Cavgt) was also derived to account for dose modifications up to each observation point. Kaplan-Meier method and the Cox proportional hazards model were employed to explore relationship between progression-free survival (PFS) an...