Cytochrome P450 inhibitor/inducer treatment patterns among patients in the United States with advanced ovarian cancer who were prescribed or were eligible for poly(adenosine diphosphate [ADP]-ribose) polymerase inhibitors in the first-line maintenance setting.

Poly(adenosine diphosphate [ADP]-ribose) polymerase inhibitors (PARPi) are metabolized either via carboxylesterase (niraparib) or cytochrome P450 (CYP) enzymes (olaparib and rucaparib). Patients with advanced epithelial ovarian cancer (aOC) who receive concomitant medication metabolized by the CYP system may be at risk of drug-drug interactions impacting PARPi efficacy and tolerability. This study investigated CYP inhibitor/inducer treatment patterns in the first-line maintenance (1Lm) setting for patients with aOC. This retrospective cohort study used de-identified databases of US patients with aOC. Eligible patients were aged ≥18 years, diagnosed with aOC between January 2015-March 2021, and received CYP inhibitors/inducers during 1Lm PARPi initiation or the eligibility window (90 days before to 120 days after first-line platinum-based therapy ended [index]). Patients were either prescribed 1Lm PARPi monotherapy (PARPi cohort) or were not prescribed any 1Lm therapy within 120 days post-index (PARPi-eligible cohort). Strong/moderate CYP inhibitors/inducers were defined as area under the plasma concentration-time curve ratio (AUCR) ≥2 or clearance ratio (CL) ≤0.5 (inhibitors), and AUCR ≤0.5 or CL ratio ≥2 (inducers). Of 1411 patients (median age 63), 158 were prescribed PARPis and 1253 were PARPi-eligible. Among the PARPi cohort, 46.2%, 48.7%, and 5.1% were prescribed niraparib, olaparib, and rucaparib, respectively. For patients prescribed olaparib or rucaparib, 42.4% also received strong and/or moderate CYP inhibitors/inducers. This real-world study indicated a considerable proportion of patients received strong and/or moderate CYP inhibitors/inducers and were prescribed PARPis metabolized by the CYP system. Understanding potential impacts of concomitant CYP inhibitors/inducers on PARPi efficacy and safety is warranted.
Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: BJR has received consulting or advisory fees from Deep6AI, AstraZeneca, and Tesaro, a GSK company; DMC declares advisory/consultancy for AstraZeneca, GSK, Clovis Oncology; speaker bureaus for AstraZeneca, GSK; and travel/accommodation/expenses from AstraZeneca, GSK; JP is an employee of GSK and holds stock/shares at GSK and Boston Scientific; AKG, JAH, and LK are employees of GSK; AAG is a former GSK employee; EXD, TW, and JS are employees of Analysis Group, which received consulting fees from GSK; RS reports honoraria from Arcus, Clovis, Genentech, GSK, Immunogen, Instil Bio, Merck, and Seagen; and advisory fees from Genentech; BJM reports consulting fees from Amgen, Aravive AstraZeneca, Clovis, GOG Foundation, Gradalis ImmunoGen Laekna Health Care, Merck, Mersana Myriad, Nucana Oncomed Oncoquest Pfizer, Roche/Genentech, GSK), speakers’ bureau fees (Clovis, Merck, Roche/Genentech, GSK), honoraria (Amgen, Aravive AstraZeneca, Clovis, GOG Foundation, Gradalis ImmunoGen Laekna Health Care, Merck, Mersana Myriad, Nucana Oncomed Oncoquest Pfizer, Roche/Genentech, GSK).
(© 2024 GSK.)