Apatinib with first-generation EGFR-TKIs as second-line treatment for patients with advanced non-small cell lung cancer with acquired resistance: a retrospective case series analysis

Abstract Background: Resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) develops in most patients with non-small cell lung cancer (NSCLC) and negates the effects of the drug. Herein we try to explore a feasible method for patients with acquired resistance to first-generation EGFR-TKIs. Methods: This study primary assessed the efficacy of first-generation EGFR-TKIs combined with low-dose apatinib (a vascular endothelial growth factorreceptor-2 (VEGFR-2) TKI) in NSCLC patients with acquired resistance to EGFR-TKIs. We retrospect the clinical date of 50 NSCLC patientssuffering from gradual disease progression following efficacious targeted therapy using first-generation EGFR-TKIs. Patients received apatinib(250 mg, p.o.) once-daily with a first-generation EGFR-TKI (gefitinib or icotinib) until disease progression or unacceptable toxicity.The primary outcome measures the proportion of patients with a disease control assessed by the investigators according to RECIST 1.1. Results: The median duration of observation was 7.5 (range, 1–20) months. The disease control rate was 90.0%, overall response rate was 32.0%. Hypertension, hand-foot syndrome, proteinuria and rash were the most common adverse events. Significant adverse events included hypertension and hemorrhage, only 2 patient quit the treatment because of adverse events. When disease progressed again after experiencing effective combined targeted therapy, patients could receive efficacious treatment with osimertinib or chemotherapy. Conclusions: Our findings suggest that adding extra apatinib to first-generation EGFR-TKIs may prolong the effective duration of efficacy of first-generation EGFR-TKI. Besides, convenience and potential therapeutic safety advantages is also the advantages of our regimen.