EGFR expression as a predictor of survival for first-line chemotherapy plus cetuximab in patients with advanced non-small-cell lung cancer: analysis of data from the phase 3 FLEX study

Pirker, 2009, Cetuximab plus chemotherapy in patients with advanced non-small-cell lung cancer (FLEX): an open-label randomised phase III trial, Lancet, 373, 1525, 10.1016/S0140-6736(09)60569-9 Roberts, 2010, Personalized medicine in non-small-cell lung cancer: is KRAS a useful marker in selecting patients for epidermal growth factor receptor-targeted therapy?, J Clin Oncol, 28, 4769, 10.1200/JCO.2009.27.4365 Stinchcombe, 2010, Targeted therapies: biomarkers in NSCLC for selecting cetuximab therapy, Nat Rev Clin Oncol, 7, 426, 10.1038/nrclinonc.2010.99 O'Byrne, 2011, Molecular biomarkers in non-small-cell lung cancer: a retrospective analysis of data from the phase 3 FLEX study, Lancet Oncol, 12, 795, 10.1016/S1470-2045(11)70189-9 Kimura, 2007, Antibody-dependent cellular cytotoxicity of cetuximab against tumor cells with wild-type or mutant epidermal growth factor receptor, Cancer Sci, 98, 1275, 10.1111/j.1349-7006.2007.00510.x Matar, 2004, Combined epidermal growth factor receptor targeting with the tyrosine kinase inhibitor gefitinib (ZD1839) and the monoclonal antibody cetuximab (IMC-C225): superiority over single-agent receptor targeting, Clin Cancer Res, 10, 6487, 10.1158/1078-0432.CCR-04-0870 Lee, 2010, Protein overexpression and gene amplification of epidermal growth factor receptor in nonsmall cell lung carcinomas: comparison of four commercially available antibodies by immunohistochemistry and fluorescence in situ hybridization study, Lung Cancer, 68, 375, 10.1016/j.lungcan.2009.07.014 Bonetti, 2000, A graphical method to assess treatment-covariate interactions using the Cox model on subsets of the data, Stat Med, 19, 2595, 10.1002/1097-0258(20001015)19:19<2595::AID-SIM562>3.0.CO;2-M Bonetti, 2004, Patterns of treatment effects in subsets of patients in clinical trials, Biostatistics, 5, 465, 10.1093/biostatistics/kxh002 Lazar, 2010, Evaluation of treatment-effect heterogeneity using biomarkers measured on a continuous scale: subpopulation treatment effect pattern plot, J Clin Oncol, 28, 4539, 10.1200/JCO.2009.27.9182 Brookmeyer, 1982, A confidence interval for the median survival time, Biometrics, 38, 29, 10.2307/2530286 Robins, 1986, Estimators of the Mantel-Haenszel variance consistent in both sparse data and large-strata limiting models, Biometrics, 42, 311, 10.2307/2531052 Meert, 2002, The role of EGF-R expression on patient survival in lung cancer: a systematic review with meta-analysis, Eur Respir J, 20, 975, 10.1183/09031936.02.00296502 Nakamura, 2006, Survival impact of epidermal growth factor receptor overexpression in patients with non-small cell lung cancer: a meta-analysis, Thorax, 61, 140, 10.1136/thx.2005.042275 Lei, 1999, Enhancement of chemosensitivity and programmed cell death by tyrosine kinase inhibitors correlates with EGFR expression in non-small cell lung cancer cells, Anticancer Res, 19, 221 Coley, 2006, Receptor tyrosine kinase (RTK) inhibition is effective in chemosensitising EGFR-expressing drug resistant human ovarian cancer cell lines when used in combination with cytotoxic agents, Biochem Pharmacol, 72, 941, 10.1016/j.bcp.2006.07.022 Hiraishi, 2008, EGFR inhibitor enhances cisplatin sensitivity of oral squamous cell carcinoma cell lines, Pathol Oncol Res, 14, 39, 10.1007/s12253-008-9020-5 Dacic, 2006, Significance of EGFR protein expression and gene amplification in non-small cell lung carcinoma, Am J Clin Pathol, 125, 860, 10.1309/H5UW6CPCWWC92241 Fontanini, 1995, Epidermal growth factor receptor (EGFr) expression in non-small cell lung carcinomas correlates with metastatic involvement of hilar and mediastinal lymph nodes in the squamous subtype, Eur J Cancer, 31A, 178, 10.1016/0959-8049(93)00421-M Ohsaki, 2000, Epidermal growth factor receptor expression correlates with poor prognosis in non-small cell lung cancer patients with p53 overexpression, Oncol Rep, 7, 603 Parra, 2004, Analysis of epidermal growth factor receptor expression as a predictive factor for response to gefitinib (‘Iressa’, ZD1839) in non-small-cell lung cancer, Br J Cancer, 91, 208, 10.1038/sj.bjc.6601923 Khambata-Ford, 2010, Analysis of potential predictive markers of cetuximab benefit in BMS099, a phase III study of cetuximab and first-line taxane/carboplatin in advanced non-small-cell lung cancer, J Clin Oncol, 28, 918, 10.1200/JCO.2009.25.2890 Lynch, 2010, Cetuximab and first-line taxane/carboplatin chemotherapy in advanced non-small-cell lung cancer: results of the randomized multicenter phase III trial BMS099, J Clin Oncol, 28, 911, 10.1200/JCO.2009.21.9618 Cappuzzo, 2005, Epidermal growth factor receptor gene and protein and gefitinib sensitivity in non-small-cell lung cancer, J Natl Cancer Inst, 97, 643, 10.1093/jnci/dji112 Felip, 2008, A phase II pharmacodynamic study of erlotinib in patients with advanced non-small cell lung cancer previously treated with platinum-based chemotherapy, Clin Cancer Res, 14, 3867, 10.1158/1078-0432.CCR-07-5186 Hirsch, 2003, Epidermal growth factor receptor in non-small-cell lung carcinomas: correlation between gene copy number and protein expression and impact on prognosis, J Clin Oncol, 21, 3798, 10.1200/JCO.2003.11.069 Rüschoff, 2011, Round robin test to evaluate the reproducibility of an immunohistochemical score with therapeutic relevance that dichotomizes non-small cell lung cancer into tumors with high and low epidermal growth factor receptor expression, J Thorac Oncol, 6, S1032 Finn, 2009, J Clin Oncol, 27, 3908, 10.1200/JCO.2008.18.1925 Harvey, 1999, Estrogen receptor status by immunohistochemistry is superior to the ligand-binding assay for predicting response to adjuvant endocrine therapy in breast cancer, J Clin Oncol, 17, 1474, 10.1200/JCO.1999.17.5.1474 Ridolfi, 2000, HER-2/neu testing in breast carcinoma: a combined immunohistochemical and fluorescence in situ hybridization approach, Mod Pathol, 13, 866, 10.1038/modpathol.3880154 Ruschoff, 2010, HER2 diagnostics in gastric cancer-guideline validation and development of standardized immunohistochemical testing, Virchows Arch, 457, 299, 10.1007/s00428-010-0952-2