SWOG S0342 and S0536: Expression of EGFR protein and markers of epithelial-mesenchymal transformation (EMT) in cetuximab/chemotherapy-treated non-small cell lung cancer (NSCLC)

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11076 Background: High EGFR gene copy number is associated with efficacy in NSCLC patients (pts) receiving combined chemotherapy and cetuximab (S0342). EGFR protein is typically overexpressed in tumors with high copy number but no consistent association has yet been demonstrated between EGFR protein expression and outcome in pts treated with chemotherapy plus cetuximab. EMT is associated with aggressive biological behavior and resistance to anti-EGFR TKI therapy in NSCLC. Our objective was to identify any association between EGFR protein and EMT and to correlate findings with pt outcomes from cetuximab/chemotherapy in SWOG trials S0342 (paclitaxel [P]-carboplatin [CB] plus sequential or concurrent cetuximab [CX]) and S0536 (P-CB-CX + bevacizumab). Methods: Paraffin sections were stained by immunoperoxidase methods using monoclonal antibodies against EGFR and the EMT markers vimentin, E-cadherin and Zeb1. Sections were scored on continuous scale ranging from 0–300 based on the H score (sum of % positive at each intensity from 0–3). Results were compared to outcome by Kaplan-Meier plot. Results: 79 samples from S0342 were evaluated for EGFR and EMT markers. 67 samples from S0536 were assessed for EGFR only. Mean EGFR H score was 153 and 137 for S0342 and S0536 respectively. At all cut points tested (scores 0, <100, <300) no association between EGFR H score and response or progression-free survival (PFS) was detected in either trial. There was a trend for overall survival and EGFR level at each cutpoint in S0536 but the results did not achieve statistical significance (15 vs 11 mos, p=0.14; 15 vs 11 mos, p=0.20 and 14 mos vs not reached, p=0.10, respectively). Vimentin (6 positive pts) was associated with a shorter PFS, HR=2.60 (1.10–6.14), p=0.03. ECAD and Vimentin were significantly inversely correlated with one another (Spearman p-value<0.01) Conclusions: EGFR protein level by IHC does not significantly correlate with efficacy parameters in chemotherapy/cetuximab-treated NSCLC pts. Patients with vimentin producing tumors (and possible other EMT markers) had shorter PFS, suggesting possible relative resistance to EGFR blockade from cetuximab. [Table: see text]