The EGFR tyrosine kinase inhibitors as second-line therapy for EGFR wild-type non-small-cell lung cancer: a real-world study in People's Republic of China.

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.