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Purpose: Pharmacokinetic studies have suggested that proton-pump inhibitors (PPI) may reduce bioavailability of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI). This study aims to examine the impact of the co-administration of EGFR-TKI and PPI on treatment outcomes in non-small cell lung cancer (NSCLC) patients.
Methods: This was a retrospective, observational study conducted at the largest ambulatory cancer center in Singapore. All patients diagnosed with NSCLC receiving EGFR-TKI (gefitinib or erlotinib) between January 2007 to December 2010 were included in this study. All traceable baseline patient characteristics from the date of EGFR-TKI initiation to the date of death or the last follow up date, whichever occurred first, were obtained from the electronic databases and medical records. Treatment outcomes measured in this study included overall survival (OS), progression-free survival (PFS) and tumor response (with or without disease progression). Cox regression analysis and multivariate logistic regression were conducted for data analysis.
Results: A total of 237 eligible patients were included in the final analysis (median age=67.0 years). Majority of the patients were female (69.2%), diagnosed with Stage 4 NSCLC (65.8%) and received gefitinib (91.6%). Two groups were formed based on PPI exposure, and PPI were concomitantly used with EGFR-TKI among 107 (45.1%) patients. Baseline characteristics were similar between these two groups. Comparing the clinical outcomes between with and without co-administration of PPI, no significant difference was observed in mean OS (13.1 vs. 12.8 months; p = 0.30), mean PFS (10.1 vs. 9.0 months, p = 0.37) or the proportion of patients without disease progression (24.5% vs. 30.0%, p = 0.24).
Conclusion: This is the largest study to date to evaluate the interaction between PPI and EGFR-TKI among NSCLC patients. Our findings suggest that concomitant use of TKI and PPI may not compromise treatment outcomes.