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 Zhang, Tong Li, Hui Li
Department of Thoracic Surgery, Beijing Institute of Respiratory Diseases, Beijing Chaoyang Hospital, Capital Medical University, Bejing, China (mainland)
Med Sci Monit 2014; 20:2666-2676
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, Randomized Controlled Trials as Topic, Receptor, Epidermal Growth Factor - genetics