Objectives: As the bioavailability of erlotinib is dependent on gastric pH, an increase in gastric pH via the concurrent use of gastric acid suppressive medications (AS) may reduce its bioavailability and efficacy. We retrospectively analyzed the BR.21 trial database to pragmatically evaluate the impact of AS use on the median plasma drug levels of erlotinib, adverse events and outcome of participants.
Methods: Monthly median plasma levels of erlotinib were compared between participants utilizing AS and those who did not using a Wilcoxon test. Interaction p-value for AS users and AS non-users was performed using a multivariate Cox model with a time-dependent covariate for AS use. Grade 2 adverse events were compared using Fisher's Exact Test.
Results: The median plasma erlotinib level was not significantly different between AS users and AS non-users, and AS use did not appear to incur a negative impact on PFS or OS (Interaction p-values: PFS p = 0.16; OS p = 0.81). AS users receiving erlotinib had a similar frequency of rash (50.5% vs. 42.0%, p = 0.08) and a statistically higher rate of diarrhea (27.9% vs. 15.6%, p = 0.001) compared to AS non-users. In addition, AS users had higher rates of infections (erlotinib arm: 33.7% vs. 20.0%, p < 0.0001; placebo arm: 22.7% vs. 10.8%, p = 0.02).
Conclusion: This retrospective analysis found that the co-administration of AS and erlotinib did not appear to have a significant impact on the median plasma drug levels or outcome.
Keywords: Bioavailability; Drug–drug interactions; Erlotinib; H2-receptor antagonist; Pharmacokinetics; Proton pump inhibitors.
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