Cytochrome P450--inhibiting/inducing Medication Use Among Patients With Advanced Ovarian Cancer (aOC) Who Received or Were Eligible for Poly(ADP-ribose) Polymerase Inhibitors (PARPis) as First-line Maintenance Therapy.

Background: As a class, PARPis work by disrupting DNA repair; however, they are metabolized by different pathways. Niraparib is metabolized by carboxylesterase-catalyzed amide hydrolysis, whereas olaparib and rucaparib are metabolized by the cytochrome P450 (CYP) system. Drugdrug interactions (DDIs) with other medications may change PARPi efficacy or safety in patients with aOC. Objective: This US-based, real-world study aimed to quantify and characterize patients with aOC who received CYP-inhibiting/inducing (CYP-i/i) medications when they initiated treatment or were eligible to receive PARPi first-line maintenance therapy (1LMT), to better understand the potential for DDIs with PARPis and other CYP-metabolized medications. Methods: This retrospective cohort study used data from Optum's de-identified Market Clarity Data with Optum® Enriched Oncology, which deterministically links medical and pharmacy claims with electronic health record data from providers across the continuum of care. Eligible patients were diagnosed with aOC between January 1, 2015, and March 31, 2021; were aged ≥18 years at end of first-line platinum-based chemotherapy (index date); had confirmed CYP-i/i medication use (≥1 claim between 90 days before to 120 days after index date); and had received or were eligible to receive PARPi 1LMT. Strong/moderate CYP-i/i medications were defined based on estimates of how much they increased/decreased drug exposure over time (area under the plasma concentration--time curve ratio). Patients in the PARPi-treated group received PARPi monotherapy for 1LMT (olaparib/rucaparib/niraparib). Patients in the PARPi-eligible group did not receive 1LMT within 120 days or start second-line treatment within 60 days of the index date. Descriptive statistics were used for patient characteristics. Results: The analysis included 1411 patients (PARPi treated, n=158; PARPi eligible, n=1253). Median age was 63 years for PARPi-treated patients and 64 years for PARPi-eligible patients. Among PARPi-treated patients, 46% (n=73) used niraparib, and 54% (n=85) used other PARPis metabolized by the CYP system (olaparib, 49% [n=77]; rucaparib, 5% [n=8]). The percentage of patients taking a strong/ moderate CYP-i/i medication was 38% (n=60) for the overall PARPi-treated group, 42% (n=36) for PARPi-treated patients who received olaparib or rucaparib, and 33% (n=414) for the PARPi-eligible group. For each group, the most common strong/moderate CYP-i/i medications were antiemetics and fluoroquinolone antibiotics (overall PARPi treated, 48% [n=29] and 28% [n=17], respectively; PARPi-treated olaparib/rucaparib, 50% [n=18] and 25% [n=9], respectively; and PARPi eligible, 41% [n=169] and 37% [n=154], respectively). Other common strong/moderate CYP-i/i medications were imidazole-related antifungals, calcium channel--blocking blood pressure medications, and topical antifungals. Conclusions: Patients with aOC may be treated with PARPi 1LMT to delay or prevent recurrence. Multiple PARPi options exist, including niraparib, which is metabolized by carboxylesterase-catalyzed amide hydrolysis, and olaparib and rucaparib, which are metabolized by the CYP system. In this analysis, 38% of PARPi-treated and 33% of PARPi-eligible patients with aOC also received medications that were strong/moderate CYP-i/i. Cotreatment with CYP-metabolized PARPis and CYP-i/i medications could potentially lead to DDIs that could alter the efficacy and tolerability of the PARPis. Additional studies are needed to understand this important issue. Funding: Funding for this study was provided by GSK. [ABSTRACT FROM AUTHOR]