title: Pooled analysis of clinical outcome for EGFR TKI-treated patients with EGFR mutation-positive NSCLC.
abstract: Patients with non-small-cell lung cancer (NSCLC) appear to gain particular benefit from treatment with epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitors (TKI) if their disease tests positive for EGFR activating mutations. Recently, several large, controlled, phase III studies have been published in NSCLC patients with EGFR mutation-positive tumours. Given the increased patient dataset now available, a comprehensive literature search for EGFR TKIs or chemotherapy in EGFR mutation-positive NSCLC was undertaken to update the results of a previously published pooled analysis. Pooling eligible progression-free survival (PFS) data from 27 erlotinib studies (n = 731), 54 gefitinib studies (n = 1802) and 20 chemotherapy studies (n = 984) provided median PFS values for each treatment. The pooled median PFS was: 12.4 months (95% accuracy intervals [AI] 11.6-13.4) for erlotinib-treated patients; 9.4 months (95% AI 9.0-9.8) for gefitinib-treated patients; and 5.6 months (95% AI 5.3-6.0) for chemotherapy. Both erlotinib and gefitinib resulted in significantly longer PFS than chemotherapy (permutation testing; P = 0.000 and P = 0.000, respectively). Data on more recent TKIs (afatinib, dacomitinib and icotinib) were insufficient at this time-point to carry out a pooled PFS analysis on these compounds. The results of this updated pooled analysis suggest a substantial clear PFS benefit of treating patients with EGFR mutation-positive NSCLC with erlotinib or gefitinib compared with chemotherapy.
authors.affiliation: Department of Medical Oncology, Instituto de Biomedicina de Sevilla (HUVR, US and CSIC) and Hospital Universitario Virgen del Rocio, Seville, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Paz-Ares
authors.forename: Denis
authors.initials: D
authors.lastname: Soulières
authors.forename: Joachim
authors.initials: J
authors.lastname: Moecks
authors.forename: Ilze
authors.initials: I
authors.lastname: Bara
authors.forename: Tony
authors.initials: T
authors.lastname: Mok
authors.forename: Barbara
authors.initials: B
authors.lastname: Klughammer
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D066246:ErbB Receptors / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D015201:Meta-Analysis as Topic; D009154:Mutation / Q000235:genetics*; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D012196:Review Literature as Topic; D015996:Survival Rate
chemical_list: D047428:Protein Kinase Inhibitors; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: afatinib; epidermal growth factor receptor (EGFR); erlotinib; first line; gefitinib; icotinib; mutation; non-small-cell lung cancer (NSCLC); tyrosine-kinase inhibitor
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