Abstract
INTRODUCTION: Clinical evidence comparing chemotherapy and tyrosine kinase inhibitors (TKIs) as second-line therapy for epidermal growth factor receptor (EGFR) wild-type non-small-cell lung cancer (NSCLC) are conflicting. METHODS: We retrospectively reviewed stage IV EGFR wild-type NSCLC patients who relapsed on first-line chemotherapy at the Shanghai Chest Hospital to compare the efficacy of TKIs and chemotherapy as second-line therapy among different clinical subgroups. RESULTS: The progression-free survival (PFS) and overall survival for patients receiving chemotherapy as second-line therapy for NSCLC were longer than patients who received TKIs. The hazard ratios (HRs) were 0.40 (P<0.001) and 0.50 (P<0.001), respectively. Subgroup analyses showed that second-line TKI therapy resulted in inferior PFS among smokers (HR =0.24, P<0.001), males (HR =0.33, P<0.001), females (HR =0.54, P=0.004), and patients with adenocarcinoma (HR =0.48, P<0.001) and nonadenocarcinoma histology (HR =0.20, P<0.001). Among never-smokers, the PFS in cohorts receiving second-line chemotherapy or TKIs was not significantly different (HR =0.70, P=0.08). CONCLUSION: These results suggest that EGFR TKI therapy was inferior compared to chemotherapy in EGFR wild-type NSCLC patients who relapsed from first-line chemotherapy; however, among never-smokers, these two treatment strategies were comparable.