Pharmacokinetics, safety, tolerability, and feasibility of apatinib in combination with gefitinib in stage IIIB-IV EGFR-mutated non-squamous NSCLC: a drug-drug interaction study

Purpose Apatinib combined with gefitinib was proven to benefit advanced EGFR-mutant NSCLC patients in first-line treatment. This study aimed to evaluate the drug-drug interaction of gefitinib and apatinib when coadministered in EGFR-mutated NSCLC patients. Methods In this phase 1b, multi-center, open-label, fixed-sequence study, the drug-drug interaction of gefitinib and apatinib was evaluated when coadministered in EGFR-mutated NSCLC patients. Patients received single-agent apatinib 500 mg QD on days 1–4. Gefitinib 250 mg QD was given on days 5–15 and combined with apatinib 500 mg QD on days 12–15. Serial blood samples were drawn on days 4 and 15. The plasma concentrations and other pharmacokinetics parameters were measured for apatinib with and without gefitinib. Results The study enrolled 22 patients and 20 were analyzed for pharmacokinetics. There were no distinct differences in apatinib C max and AUC 0−τ with versus without gefitinib (geometric LSM ratio, 0.96 [90% CI 0.84–1.10] for C max and 1.12 [90% CI 0.96–1.30] for AUC 0−τ ). Similar PFS and grade of treatment-emergent adverse events (TEAEs) were found between different C max and AUC 0−τ of apatinib and gefitinib at 500 mg apatinib and 250 mg gefitinib dose levels. Conclusions Apatinib pharmacokinetics parameters were not significantly changed when coadministered with gefitinib. All TEAEs were manageable, and there was no need to change the dose level when combining apatinib and gefitinib (ClinicalTrials.gov identifier: NCT04390984, May 18, 2020).