Mapping drug-drug interactions in pharmacokinetic boosting of olaparib

In pharmacokinetic (PK) boosting, an intentional drug-drug interaction (DDI) is used to increase the exposure of another drug. PK boosting of the anticancer drug olaparib with the potent Cytochrome P450 (CYP3A)-inhibitor cobicistat can improve oral bioavailability, tolerability, and affordability. Cancer patients often present with many comedications that can also be affected by CYP3A-inhibitors, which requires thorough assessment of DDIs. This may hamper the feasibility of boosting. Here, we report potential DDIs between cobicistat and comedication in a retrospective cohort of patients treated with olaparib and how these DDIs can be mitigated.

Patients who received olaparib between April 2017 and February 2024 were included. Comedications at the start of olaparib treatment were screened for potential DDIs with cobicistat if PK boosting would have been initiated in these patients. Relevant DDIs were reviewed by an expert panel of pharmacists and clinical pharmacologists and recommendations for mitigating interventions were formulated.

In total, 97 patients were included with a median of six concomitant medications per patient (range 0-13). 59% of patients presented with at least one relevant DDI. With the recommended interventions, 14% of patients had a DDI that required additional monitoring and 1% had a contra-indicated DDI.

DDIs were highly prevalent when PK boosting of olaparib is applied. Nonetheless, nearly all DDIs could be mitigated by an intervention and most interventions could be applied without additional monitoring. PK boosting of olaparib with cobicistat is thus considered feasible with appropriate expertise and resources.