Retrospective Evaluation of Drug-Drug Interactions With Erlotinib and Gefitinib Use in the Military Health System
Background: Erlotinib and gefitinib are epidermal growth factor receptor–tyrosine kinase inhibitors approved for non–small cell lung cancer treatment by the US Food and Drug Administration. Drug-drug interactions (DDIs) with these agents are vague and poorly understood. Because DDIs can have an effect on clinical outcomes, we aimed to identify drugs that interact with erlotinib or gefitinib and describe their clinical manifestations.
Methods: A retrospective analysis was performed on the health records of patients in the US Department of Defense Cancer Registry (retrieved September 2021), Comprehensive Ambulatory/Professional Encounter Records, and Pharmacy Data Transaction Service database (both retrieved May 2022). Patients’ medical history, diagnoses, and demographics were extracted and analyzed for differences in adverse effects when these agents were used alone vs concomitantly with other prescription drugs. Patients’ diagnoses and prescription drug use were extracted to compare completed vs discontinued treatment groups, identify medications commonly co-administered with erlotinib or gefitinib, and evaluate DDIs with antidepressants.
Results: Of 387 patients using erlotinib, 264 completed treatments; 28 of 33 patients using gefitinib completed treatment. The P value for erlotinib discontinuation when used alone vs concomitantly was < .001, and the P value for gefitinib discontinuation was .06. Patients who took erlotinib or gefitinib concomitantly with a greater number of prescription drugs had a higher rate of treatment discontinuation than those who received fewer medications. Patients in the completed group received 1 to 75 prescription drugs, and those in the completed group were prescribed 3 to 103. Those who discontinued treatment had more diagnosed medical issues than those who completed treatment.
Conclusions: This review cannot conclude that concomitant use with prescription drug(s) resulted in erlotinib or gefitinib discontinuation. There were no significant DDIs determined between erlotinib or gefitinib and antidepressants.
Methods
The DoD Cancer Registry Program was established in 1986 by the Assistant Secretary of Defense for Health Affairs. The registry currently contains data from 1998 to 2023. CAPER and PDTS are part of the MHS Data Repository/Management Analysis and Reporting Tool database. Each observation in the CAPER record represents an ambulatory encounter at a military treatment facility (MTF). CAPER records are available from 2003 to 2023.
Each observation in the PDTS record represents an outpatient prescription filled for an MHS beneficiary at MTFs through the TRICARE mail-order program or a retail pharmacy in the United States. Missing from this record are prescriptions filled at civilian pharmacies outside the United States and inpatient pharmacy prescriptions. The MHS Data Repository PDTS record is available from 2002 to 2023. The Composite Health Care System—the legacy system—is being replaced by GENESIS at MTFs.
Data Extraction Design
The study design involved a cross-sectional analysis. We requested data extraction for erlotinib and gefitinib from 1998 to 2021. Data from the DoD Cancer Registry were used to identify patients who received cancer treatment. Once patients were identified, the CAPER database was searched for diagnoses to identify other health conditions, while the PDTS database was used to populate a list of prescription medications filled during chemotherapy treatment.
Data collected from the Joint Pathology Center included cancer treatment (alone or concomitant), cancer information (cancer types and stages), demographics (sex, age at diagnosis), and physicians’ comments on AEs. Collected data from the MHS include diagnosis and filled prescription history from initiation to completion of the therapy period (or a buffer of 6 months after the initial period). We used all collected data in this analysis. The only exclusion criterion was a provided physician’s note commenting that the patient did not use erlotinib or gefitinib.
Data Extraction Analysis
The Surveillance, Epidemiology, and End Results Program Coding and Staging Manual 2016 and the International Classification of Diseases for Oncology (ICD-O) were used to decode disease and cancer types.15,16 Data sorting and analysis were performed using Microsoft Excel. The percentage for the total was calculated by using the total number of patients or data available within the gefitinib and erlotinib groups divided by total number of patients or data variables. The subgroup percentage was calculated by using the number of patients or data available within the subgroup divided by the total number of patients in that subgroup.
In alone vs concomitant and completed vs discontinued treatment groups, a 2-tailed, 2-sample z test was used to calculate P to determine statistical significance (P < .05) using a statistics website.17 Concomitant was defined as erlotinib or gefitinib taken with other medication(s) before, after, or at the same time as cancer therapy. For the retrospective data analysis, physicians’ notes with “.”, “,”, “/”, “;”, (period, comma, forward slash, semicolon) or space between medication names were interpreted as concurrent, while “+”, “-/+” (plus, minus/plus), or and between drug names were interpreted as combined. Completed treatment was defined as erlotinib or gefitinib as the last medication the patient took without recorded AEs; switching or experiencing AEs was defined as discontinued treatment.
