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

Wei-Xiang Qi,Yuan-Jue Sun,Ai-Na He,Yang Yao,Da-Liu Min,Feng Lin,Li-Na Tang,Zan Shen

doi:10.7314/apjcp.2012.13.10.5177

Wei-Xiang Qi, Yuan-Jue Sun + Show 6 more

Open Access

PDF Available

https://doi.org/10.7314/apjcp.2012.13.10.5177

Copy DOI

Export

Save

Cite

Journal: Asian Pacific Journal of Cancer Prevention	Publication Date: Oct 31, 2012
Citations: 45	License type: cc-by

Abstract
Highlights/Summary
Full-Text PDF
Similar Papers

Abstract

Listen

To compare the efficacy and safety of epidermal growth factor receptor tyrosine kinase inhibitor monotherapy (EFGR-TKIs: gefitinib or erlotinib) with standard second-line chemotherapy (single agent docetaxel or pemetrexed) in previously treated advanced non-small-cell lung cancer (NSCLC). We systematically searched for randomized clinical trials that compared EGFR-TKI monotherapy with standard second-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 4 toxicities. 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 included trials. Eight randomized controlled trials (totally 3218 patients) were eligible. Our meta-analysis results showed that EGFR-TKIs were comparable to standard second-line chemotherapy for advanced NSCLC in terms of overall survival (HR 1.00, 95%CI 0.92-1.10; p=0.943), progression-free survival (HR 0.90, 95%CI 0.75-1.08, P=0.258) and 1-year-survival rate (RR 0.97, 95%CI 0.87-1.08, P=0.619), and the overall response rate was higher in patients who receiving EGFR-TKIs(RR 1.50, 95%CI 1.22-1.83, P=0.000). Sub-group analysis demonstrated 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 OS and 1-year SR. Furthermore, there were fewer incidences of grade 3 or 4 neutropenia, febrile neutropenia and neurotoxicity in EGFR-TKI monotherapy group, excluding grade 3 or 4 rash. Both interventions had comparable efficacy as second-line treatments for patients with advanced NSCLC, and EGFR-TKI monotherapy was associated with less toxicity and better tolerability. Moreover, our data also demonstrated that EGFR- TKI monotherapy tended to be more effective in East Asian patients in terms of PFS and ORR compared with standard second-line chemotherapy. These results should help inform decisions about patient management and design of future trials.

Highlights

Lung cancer is still a leading cause of cancer-related deaths worldwide with a 5-year survival of less than 15% (Parkin et al, 2002; Schiller et al, 2002; Kim et al, 2012)
Our meta-analysis results showed that EGFR-TKIs were comparable to standard second-line chemotherapy for advanced non-small-cell lung cancer (NSCLC) in terms of overall survival (HR 1.00, 95%confidence intervals (CI) 0.92-1.10; p=0.943), progression-free survival (HR 0.90, 95%CI 0.75-1.08, P=0.258) and 1-year-survival rate (RR 0.97, 95%CI 0.87-1.08, P=0.619), and the overall response rate was higher in patients who receiving EGFR-TKIs(RR 1.50, 95%CI 1.22-1.83, P=0.000)
Sub-group analysis demonstrated that EGFR-TKI monotherapy significantly improved progression-free survival (PFS) (HR 0.73, 95%CI: 0.55-0.97, p=0.03) and overall response rate (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 overall survival (OS) and 1-year SR

Summary

Introduction

Lung cancer is still a leading cause of cancer-related deaths worldwide with a 5-year survival of less than 15% (Parkin et al, 2002; Schiller et al, 2002; Kim et al, 2012). Because the majority of people diagnosed with non-small cell lung cancer (NSCLC) are unsuitable for surgery, chemotherapy remains the cornerstone of treatment and prolongs survival with a positive impact on quality of life. Of note is that approximately 50% of patients progressing to first-line treatment still have a good performance status, which would make them suitable for second-line therapy (Stinchcombe et al, 2009). Docetaxel and pemetrexed are still considered as standard second-line therapy in patients with good performance status (Fossella et al, 2000; Shepherd et al, 2000; Rossi et al, 2009), there is still much room for improvement in terms of efficacy as well as toxicity.

Methods

Results

Conclusion