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15 December 2014 : Special report  

Efficacy of EGFR Tyrosine Kinase Inhibitors in Non-Small-Cell Lung Cancer Patients with/without EGFR-Mutation: Evidence Based on Recent Phase III Randomized Trials

Wen-Qian ZhangABCDEF, Tong LiBCDEF, Hui LiABCDEFG

DOI: 10.12659/MSM.892476

Med Sci Monit 2014; 20:2666-2676

Abstract

Background: EGFR mutation might be a predictive factor for applying EGFR-tyrosine kinase inhibitors (EGFR-TKIs, including gefitinib, erlotinib and afatinib) in non-small-cell lung cancer (NSCLS) patients. Thus, it is necessary to pool previous trials to compare the effect of EGFR-TKIs versus cytotoxic chemotherapy in EGFR mutation positive (mut+) and negative (mut–) patients. Material and Methods: This study identified 8 first-line and 9 second-line phase III trials in databases. Hazard ratio (HR) was pooled to assess the risk of progression-free survival (PFS), and overall survival (OS), while odds ratio (OR) was pooled to assess objective response, disease control, and toxicity of EGFR-TKIs verses chemotherapy. Results: In EGFR mut+ patients, EGFR-TKIs were associated with significantly lower risk of disease progression in the first-line setting, but this trend was only observed in the gefitinib group, not in the erlotinib group in the second-line setting. In EGFR mut– patients, gefitinib and erlotinib had significantly higher risk of disease progression in first-line and second-line setting, respectively. Compared with chemotherapy, the effects of EGFR-TKIs on OS in both first-line and second-line settings were not evident. Regarding toxicity, EGFR-TKIs had significantly higher risk of rash and lower hematological toxicity compared with chemotherapy. Conclusions: All of the 3 EGFR-TKIs and gefitinib alone regimens had better effects in prolonging PFS in EGFR mut+ patients in first-line and second-line setting, respectively, but chemotherapy seemed more effective in EGFR mut- patients than EGFR-TKIs. Therefore, accurate identification of EGFR mutation status is useful to decide on an appropriate regimen for treatment of NSCLC patients.

Keywords: Carcinoma, Non-Small-Cell Lung - genetics, Clinical Trials, Phase III as Topic, Disease-Free Survival, Lung Neoplasms - genetics, Mutation - genetics, Protein Kinase Inhibitors - therapeutic use, Receptor, Epidermal Growth Factor - genetics

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750