Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have been proved as an effective treatment of advanced non-small-cell lung cancer patients with EGFR mutations. However, resistance to EGFR-TKIs develops in most patients and leads to eventual loss of efficacy. Nowadays combined therapy inhibiting EGFR and vascular endothelial growth factor (VEGF) pathways has become a promising therapy in the treatment of advanced non-small-cell lung cancer. This study aims to assess the efficacy and safety of the addition of low dose of apatinib, a kind of TKIs targeting vascular endothelial growth factor receptor 2 (VEGFR-2), to first-generation EGFR-TKIs for advanced non-small cell lung cancer with acquired resistance to first-generation EGFR-TKIs.
We retrospectively assessed the efficacy and safety of patients with non-small cell lung cancer who had gradual progression after experiencing effective targeted therapy with first-generation EGFR-TKIs. Patients received apatinib 250 mg once daily and gefitinib 250mg once daily or icotinib 125mg thrice daily until disease progression again or unacceptable toxicity occurs.
The study group comprised 33 Chinese patients, among whom 15 (45.5%) were males and 20 (60.6%) were non-smokers. The median duration of combined therapy was 5.5 month. 17 patients (51.5%) had a partial response (PR) and 13 patients had stable disease (SD). The overall response rate was 51.5%. 21 cases of adverse events were observed in this study. The incidence of severe adverse events was only 3.0%. The incidence of adverse events in patients decreased in hypertension, rash, proteinuria, hand-foot syndrome, gastrointestinal reaction, mucosal inflammation, bleeding, alanine aminotransferase increased and hypoovarianism.
The addition of low dose of apatinib to gefitinib or icotinib can significantly inhibit tumor growth and improve the progression-free survival of patients received first-generation EGFR-TKIs. Potential advantage in safety were identified which warrant further validation.
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All authors have declared no conflicts of interest.