Comparison of the Efficacy and Safety of EFGR TyrosineKinase Inhibitor Monotherapy with Standard Second-line Chemotherapy in Previously Treated Advanced Non-small-cell Lung Cancer: a Systematic Review and Meta-analysis

Purpose: To compare the efficacy and safety of epidermal growth factor receptor tyrosine kinaseinhibitormonotherapy (EFGR-TKIs: gefitinib or erlotinib) with standard second-line chemotherapy (single agentdocetaxel or pemetrexed) in previously treated advanced non-small-cell lung cancer (NSCLC).
Methods: Wesystematically searched for randomized clinical trials that compared EGFR-TKI monotherapy with standardsecond-line chemotherapy in previously treated advanced NSCLC. The end points were overall survival (OS),progression-free survival (PFS), overall response rate (ORR), 1-year survival rate (1-year SR) and grade 3 or 4toxicities. The pooled hazard ratio (HR) or risk ratio (RR), with their corresponding 95% confidence intervals(CI) were calculated employing fixed- or random-effects models depending on the heterogeneity of the includedtrials.
Results: Eight randomized controlled trials (totally 3218 patients) were eligible. Our meta-analysis resultsshowed that EGFR-TKIs were comparable to standard second-line chemotherapy for advanced NSCLC interms of overall survival (HR 1.00, 95%CI 0.92-1.10; p=0.943), progression-free survival (HR 0.90, 95%CI0.75-1.08, P=0.258) and 1-year-survival rate (RR 0.97, 95%CI 0.87-1.08, P=0.619), and the overall responserate was higher in patients who receiving EGFR-TKIs(RR 1.50, 95%CI 1.22-1.83, P=0.000). Sub-group analysisdemonstrated that EGFR-TKI monotherapy significantly improved PFS (HR 0.73, 95%CI: 0.55-0.97, p=0.03)and ORR (RR 1.96, 95%CI: 1.46-2.63, p=0.000) in East Asian patients, but it did not translate into increase in OSand 1-year SR. Furthermore, there were fewer incidences of grade 3 or 4 neutropenia, febrile neutropenia andneutrotoxicity in EGFR-TKI monotherapy group, excluding grade 3 or 4 rash.
Conclusion: Both interventions hadcomparable efficacy as second-line treatments for patients with advanced NSCLC, and EGFR-TKI monotherapywas associated with less toxicity and better tolerability. Moreover, our data also demonstrated that EGFRTKImonotherapytended to be more effective in East Asian patients in terms of PFS and ORR compared withstandard second-line chemotherapy. These results should help inform decisions about patient management anddesign of future trials.