Gefitinib vs. chemotherapy as first-line therapy in advanced non-small cell lung cancer: Meta-analysis of phase III trials

• Published in: Lung cancer (Amsterdam, Netherlands) Vol. 74; no. 3; pp. 469 - 473
• Main Authors: Ku, Geoffrey Y, Haaland, Benjamin A, de Lima Lopes, Gilberto
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ireland Ltd 01.12.2011; Elsevier
• Subjects: Adenocarcinoma; Biological and medical sciences; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - mortality; Carcinoma, Non-Small-Cell Lung - pathology; Carcinoma, Non-Small-Cell Lung - physiopathology; Chemotherapy; Clinical Trials, Phase III as Topic; Drug Therapy; Female; Gefitinib; Hematology, Oncology and Palliative Medicine; Humans; Japan; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Lung Neoplasms - mortality; Lung Neoplasms - pathology; Lung Neoplasms - physiopathology; Male; Medical sciences; Meta-analysis; Middle Aged; Mutation - genetics; Neoplasm Staging; Non-small cell lung cancer; Pneumology; Pulmonary/Respiratory; Quinazolines - pharmacology; Quinazolines - therapeutic use; Randomized trial; Receptor, Epidermal Growth Factor - antagonists & inhibitors; Receptor, Epidermal Growth Factor - genetics; Smoking; Survival Analysis; Tumors; Tumors of the respiratory system and mediastinum; Japan; Adenocarcinoma; Chemotherapy; Randomized trial; Gefitinib; Non-small cell lung cancer; Meta-analysis; Phase III trial; Lung disease; Respiratory disease; Malignant tumor; non-small cell lung carcinoma; Randomization; Treatment; Cancerology; Bronchus disease; Cancer; Pneumology
• ISSN: 0169-5002; 1872-8332
• DOI: 10.1016/j.lungcan.2011.04.008

Abstract Background Gefitinib is an oral tyrosine kinase inhibitor against the epidermal growth factor receptor (EGFR). It has been shown to be active in patients with advanced non-small cell lung cancer (NSCLC) whose tumors contain EGFR mutations. Methods We performed a meta-analysis of four randomized studies that compared gefitinib with chemotherapy in the first-line treatment of patients with advanced NSCLC: IPASS, North-East Japan, West Japan and first-SIGNAL studies. Patients were selected either on the basis of known EGFR mutations or based on clinicopathologic criteria – non-smokers with adenocarcinomas – associated with increased likelihood of EGFR mutations. Results Nearly 2000 patients were enrolled on these four trials. Median ages ranged from 57 to 64 years. Seventy-six percent were women and 86% were non-smokers. Overall, gefitinib was associated with significantly less toxicity than chemotherapy and improved quality-of-life. Gefitinib also produced higher response rates in the EGFR mutation-positive patients (72% vs. 38%, odds ratio 4.04, p < 10−15 ), as well as improved progression-free survival (PFS; hazard ratio 0.45, p < 10−16 ). Overall survival (OS) was not significantly different between treatment groups ( p = 0.35). Conclusions This meta-analysis confirms the results of each individual study and narrows the confidence intervals of these results. In patients with known EGFR mutations or whose tumors are likely to harbor a mutation, upfront gefitinib or chemotherapy are associated with similar OS. Gefitinib is associated with less fatigue, myelosuppression and nausea than chemotherapy (but produces more skin rash, diarrhea and pneumonitis). Patients receiving gefitinib have improved quality-of-life compared to those receiving chemotherapy, making it an appropriate first-line choice.