Exposure–Response Analyses of Olaparib in Real-Life Patients with Ovarian Cancer

Background Olaparib is given in a fixed dose of twice-daily 300 mg in patients who are diagnosed with ovarian cancer, breast cancer, prostate cancer or pancreas cancer and has a high interpatient variability in pharmacokinetic exposure. The objective of this study was to investigate whether pharmacokinetic exposure of olaparib is related to efficacy and safety in a real-life patient’ cohort. Methods A longitudinal observational study was conducted in patients who received olaparib for metastatic ovarian cancer of whom pharmacokinetic samples were collected. A Kaplan–Meier analyses was used to explore the relationship between olaparib exposure, measured as (calculated) minimum plasma concentrations (C min ), and efficacy, Univariate and multivariate cox-regression analyses were performed. Also, the C min of patients who experienced toxicity was compared with patients who did not experience any toxicity. Results Thirty-five patients were included in the exposure-efficacy analyses, with a median olaparib C min of 1514 ng/mL. There was no statistical significant difference in PFS of patients below and above the median C min concentration of olaparib, with a hazard ratio of 1.06 (95% confidence interval: 0.46–2.45, p = 0.9)). For seven patients pharmacokinetic samples were available before toxicity occurred, these patients had a higher C min of olaparib in comparison with patients who had not experienced any toxicity ( n = 33), but it was not statistically significant ( p = 0.069). Conclusions Our study shows that exposure of olaparib is not related to PFS. This suggests that the approved dose of olaparib yields sufficient target inhibition in the majority of patients.