Combination of EGFR-TKIs with chemotherapy versus chemotherapy or EGFR-TKIs alone in advanced NSCLC patients with EGFR mutation

Purpose: Both epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) and chemotherapy are widely applied for the treatment of advanced non-small-cell lung cancer (NSCLC) with EGFR mutations, and the combination of EGFR-TKIs and chemotherapy has been used for advanced NSCLC patients; however, little is known about the efficacy of the direct comparison among them. Patients and methods: The demographic and clinical characteristics of 92 patients harboring advanced NSCLC with EGFR mutation were retrospectively reviewed. We evaluated the effects of EGFR-TKIs, chemotherapy, and EGFR-TKIs plus chemotherapy on advanced NSCLC patients with EGFR mutations, and the efficacy of combination of chemotherapy and EGFR-TKIs vs chemotherapy or EGFR-TKIs alone in advanced NSCLC patients was evaluated. Results: The statistical results showed that the intercalated combination of EGFR-TKIs plus chemotherapy significantly improved progression-free survival (PFS; HR, 1.76; 95% CI 1.03-3.01; P=0.036; median, 20.5 vs 16 months) compared with EGFR-TKI monotherapy, but no difference in overall survival (OS) was observed between these two groups (HR, 1.52; 95% Cl 0.81 -2.83; P=0.19; median, 36 vs 29 months). However, patients who received the combination of chemotherapy and EGFR-TKIs had longer PFS (HR, 2.78; 95% CI 1.57-4.93; P< 0.0001; median, 20.5 vs 12 months) as well as OS(HR, 2.86; 95% Cl 1365.27; P=0.001; median, 36 vs 18 months) than those who received chemotherapy alone. Toxicities were mild among the three treatment groups. Rash and diarrhea were common adverse events (AEs) in the EGFR-TKI group, anemia and nausea in the chemotherapy group, and anemia and diarrhea in the combination group. Conclusion: This study demonstrated that the combination of chemotherapy with EGFR-TKIs as first-line treatment has a significant effect on PFS in patients with advanced NSCLC whose tumors harbor activating EGFR mutations. The combination treatment had more toxicity, but was clinically manageable.