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.

Automated summary

This study aimed to investigate whether the pharmacokinetic exposure of olaparib is associated with its efficacy and safety. The results showed that the exposure of olaparib is not related to PFS, suggesting that the approved dose can achieve sufficient target inhibition in the majority of patients.