PT-006 - PHARMACOKINETIC DRUG-DRUG INTERACTION POTENTIAL OF ORAL ANTICANCER DRUGS.

F. Alhurayri¹, N. Powell², I. Younis³, S. Jalal², T. Logan², S. Quinney^4,5, Z. Desta⁶, T. Skaar⁷, J. Tisdale¹, T. Shugg⁷; ¹Purdue University, West Lafayette, IN, US, ²Indiana University School of Medicine, Indianapolis, IN, US, ³Merck, Rahway, NJ, USA, ⁴Division of Clinical Pharmacology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA, ⁵Department of OB/GYN, Indiana University School of Medicine, Indianapolis, IN, USA, ⁶Division of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, IN, USA, ⁷Division of Clinical Pharmacology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.

Background: Since cancer patients are commonly prescribed multiple concomitant medications, managing drug-drug interactions (DDIs) is critical for optimizing efficacy and minimizing toxicity of oral anticancer (OAC) drugs. Our study objectives were to (1) determine DDI mechanisms for OACs and (2) assess the prevalence of potential DDIs in a cohort of adults with advanced solid cancers.

Methods: Objective 1: DDI mechanisms for 101 OACs approved for solid or hematological cancer from January 1997 through January 2023 were determined from clinical DDI studies and pharmacokinetic modeling analyses obtained from FDA drug labels and primary literature review. Drugs were classified as having DDI potential if they were strong or moderate inhibitors, inducers, or sensitive substrates for major cytochrome P450 (CYP) enzymes or drug transporters or if their exposure was altered by ≥50% during co-administration with acid reducers. Objective 2: A retrospective review of electronic health records of 3697 patients discussed at an institutional solid tumor board were reviewed to detect potential DDIs, defined as overlapping prescriptions of OACs with relevant interacting drugs.

Results: Objective 1: FDA labels were reviewed for 101 OACs, and 233 studies were extracted from the primary literature, yielding a total of 771 drug-drug pairs for analysis. Seventy-nine OACs had DDI potential involving at least one mechanism. The most common DDI mechanisms were CYP3A substrates, CYP3A perpetrators, and victims with acid reducers (40.6%, 17.8%, and 12.9% of OACs, respectively). Our primary literature search detected clinically relevant DDI mechanisms without actionable recommendations in the FDA-approved drug labels for 8 drugs. Objective 2: Nearly half of patients (47.5%) were prescribed ≥1 OACs, among which 21.2% of patients had ≥1 potential DDI. Of patients with ≥1 potential DDI, 47.5%, 25.2%, and 21.4% had potential DDIs related to OACs being CYP3A substrates, PPI victims, and CYP3A perpetrators, respectively. The prevalence of potential DDIs of the most widely prescribed OACs is shown in Table 1.

Conclusion: The majority of OACs have one or more mechanisms of potential DDI, and we infer that 1 in 5 patients in solid tumor board populations have a possible clinically relevant DDI. These findings demonstrate the importance of identifying and managing DDIs with OACs.