K-Ras mutation (mut), EGFR-related, and exploratory markers as response predictors of cetuximab in first-line advanced NSCLC: Retrospective analyses of the BMS099 trial

作者：Shirin Khambata‐Ford, Christopher Harbison, Donald Woytowitz, M. Awad, Christine E. Horak, L. Xu, Shaker R. Dakhil, Robert C. Hermann, Thomas J. Lynch, Martin R. Weber · 发表于：Journal of Clinical Oncology · 年份：2009 · DOI：10.1200/jco.2009.27.15_suppl.8021 · 被引用次数：19 · 研究领域：Lung Cancer Treatments and Mutations、Cancer Genomics and Diagnostics、Colorectal Cancer Treatments and Studies

8021 Background: This phase III study investigated cetuximab (C) plus taxane/carboplatin (TC) in 1 st -line advanced NSCLC. Progression-free survival (PFS) was not significantly different with the addition of C to TC; response rate (RR) was significantly higher; median overall survival (OS) was longer, with a difference (not statistically significant) similar in magnitude to the significant OS improvement from FLEX (cisplat/vinorelb±C). Potential patient-selection markers were analyzed, including mut in K-Ras, EGFR mut and gene copy number (GCN), EGFR protein expression, and gene expression profiles. Methods: Chemonaïve patients (pts) with stage IIIB/IV NSCLC (any histology or EGFR expression status) were randomized to TC±C. K-Ras gene exon 2, and EGFR exons 18–21 were sequenced bidirectionally using formalin-fixed paraffin embedded tissue-derived genomic DNA. EGFR GCN was measured by fluorescence in situ hybridization (FISH) and EGFR protein expression by immunohistochemistry (IHC). Exploratory expression profiling studies using Affymetrix GeneChip are ongoing. Analyses were blinded to clinical outcome. The relationships between biomarker status and efficacy were assessed with log-rank tests per study arm for treatment-specific effects, and across the total evaluable population. Results: Samples from 225/676 randomized pts were available; 35/202 (17%) had K-Ras mut, 17/167 (10%) had EGFR mut, 54/104 (52%) were EGFR FISH+, 131/148 (89%) were EGFR IHC+. There were no significa...