Effects of Acid-Reducing Agents on the Pharmacokinetics of Lazertinib in Patients with EGFR Mutation-Positive Advanced Non-Small-Cell Lung Cancer

Introduction Lazertinib is an irreversible, mutant-selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI). Co-administration of TKIs with acid-reducing agents (ARAs) can lead to potential drug–drug interactions, which decreases solubility and absorption of TKIs and is ultimately associated with reduced efficacy of TKIs. This retrospective analysis evaluated the effect of ARAs on the pharmacokinetics of lazertinib using data obtained from patients with advanced EGFR mutation-positive non-small-cell lung cancer. Methods In a total of 234 patients with lazertinib pharmacokinetics observed at steady state, dose-normalized (DN) area under the concentration–time curve (AUC ss ), maximum concentration ( C max,ss ), and/or trough concentration on day 15 ( C D15 ) were compared between a group receiving ARA concomitantly for at least 4 days (ARA group) and another group not receiving ARA (non-ARA group) in a dose-proportional range. Additionally, a comparison of pharmacokinetic parameters at a therapeutic dose of 240 mg once daily was evaluated. Results Geometric mean ratios (GMRs) with 90% confidence intervals (CIs) of ARA group to non-ARA group for DNAUC ss , DNC max,ss , and DNC D15 at 40 mg to 320 mg once daily showing the dose proportionality were 0.8743 (0.7285–1.0493), 0.9035 (0.7482–1.0910), and 0.9126 (0.7364–1.1311), respectively. GMRs with 90% CIs for AUC ss , C max,ss , and C D15 at 240 mg were 0.9136 (0.6637–1.2576), 0.9012 (0.6703–1.2116), and 0.8850 (0.6463–1.2118), respectively. Conclusion All pharmacokinetic parameters were not significantly different between the two groups ( p values > 0.05), indicating that co-administered ARAs did not significantly affect the steady state pharmacokinetics of lazertinib. Therefore, no dose adjustment of lazertinib is required in patients receiving concomitant ARAs. ClinicalTrials.gov identifiers NCT03046992, NCT04075396.