Apatinib With Gefitinib Or Icotinib For Advanced Non-small Cell Lung Cancer Patients With Acquired Resistance To First-generation EGFR-TKIs

Resistance to epidermal growth factor receptor(EGFR)tyrosine kinase inhibitors(TKIs)develops in most non-small cell lung cancer(NSCLC)patients treated with these agents,and leads to eventual loss of efficacy.This study assessed the efficacy and toxicity of first-generation EGFR-TKIs in addition with low-dose apatinib,a VEGF receptor-2(VEGFR-2)TKI,in NSCLC patients with acquired resistance to EGFR-TKIs.We retrospectively evaluated 39 NSCLC patients experiencing gradual progression following effective targeted therapy using first-generation EGFR-TKIs.Patients received oral apatinib(250 mg)once daily with a first-generation EGFR-TKI(gefitinib or icotinib)until disease progression or unacceptable toxicity.Median observation time was 8.9 months(range,1.5-16.9 months).The disease control rate was 90.6%and overall response rate was 35.6%.14(35.6%)patients exhibited a partial response,21(53.8%)had stable disease,and 4(10.4%)experienced disease progression.24 disease progressions again were observed after experiencing effective combined targeted therapy.Hypertension,rash,and proteinuria were the most common adverse events.Significant adverse events included one grade 4 hypertension and one grade 3 hemorrhage.One patient discontinued therapy due to uncontrollable hypertension.Our findings suggest that apatinib in addition with icotinib or gefitinib may prolong the duration of first-generation EGFR-TKI effectiveness.Besides,compared with other regimens targeting multiple molecular pathways,convenience and potential therapeutic safety advantages are implied in our regimen.