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

Bobbie J Rimel; Dana M Chase; Jessica Perhanidis; Armen A Ghazarian; Ella Xiaoyan Du; Travis Wang; Jinlin Song; Amanda K Golembesky; Jean A Hurteau; Linda Kalilani; Ritu Salani; Bradley J Monk

doi:10.1016/j.gore.2024.101332

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

Gynecol Oncol Rep. 2024 Feb 7:51:101332. doi: 10.1016/j.gore.2024.101332. eCollection 2024 Feb.

Authors

Affiliations

¹ Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
² Gynecologic Oncology Division, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
³ Value Evidence and Outcomes, GSK, Waltham, MA, USA.
⁴ Value Evidence and Outcomes, GSK, Rockville, MD, USA.
⁵ Analysis Group, Los Angeles, CA, USA.
⁶ Analysis Group, Boston, MA, USA.
⁷ Value Evidence and Outcomes, GSK, Durham, NC, USA.
⁸ US Medical Affairs, GSK, Waltham, MA, USA.
⁹ HonorHealth Research Institute, University of Arizona, Creighton University, Phoenix, AZ, USA.

Abstract

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.

Keywords: Advanced ovarian cancer; CYP450 inhibitor/inducer; Drug interactions; Poly(ADP ribose) polymerase inhibition.