Talazoparib Exposure-Efficacy Analysis in Patients With Advanced Breast Cancer and Germline BRCA1/2 Mutations in the EMBRACA Trial

In the phase 3 EMBRACA trial, treatment with the poly(ADP-ribose) polymerase inhibitor, talazoparib, led to significantly improved progression-free survival (PFS) compared with chemotherapy (hazard ratio, 0.54; 95% confidence interval, 0.41-0.71; P <.0001). We conducted an exposure-efficacy analysis using EMBRACA data from 285 patients who were treated with talazoparib and had available pharmacokinetic parameters to evaluate the effect of talazoparib exposure (time-varying average talazoparib concentration [C_avg,t]) and other baseline variables on PFS. Graphical examination of the relationship between C_avg,t and PFS and a Cox proportional model were used. Exposure-response analyses showed that higher talazoparib exposure, absence of visceral disease, lower baseline lactate dehydrogenase levels, and disease-free interval >12 months were independent covariates associated with longer PFS. The association of talazoparib exposure with PFS (higher exposure, longer PFS) suggests the recommended starting dose of 1 mg once daily (the maximum tolerated dose) is appropriate.