Predictive Biomarkers and Personalized Medicine High EGFR Gene Copy Number and Skin Rash as Predictive Markers for EGFR Tyrosine Kinase Inhibitors in Patients with Advanced Squamous Cell Lung Carcinoma

Purpose: This study aimed to search for predictors of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) efficacy in previously treated patients with advanced squamous cell lung carcinoma in which EGFR mutations are very rare. Experimental Design: EGFR gene copy numbers were assessed by FISH and evaluated as predictors of EGFR-TKI efficacy in71patientswith advanced squamous cell lung cancerwho received gefitinibor erlotinib as a second-line or higher therapy. The tumors were classified into EGFR/FISH-positive (high polysomy/ gene amplification) and EGFR/FISH-negative (other) groups. Results: EGFR/FISH was positive in 19 (26.7%) patients. Only EGFR/FISH positive status was correlated with the EGFR-TKIs response (EGFR/FISHþ vs. EGFR/FISH , 26.3% vs. 2.0%; P1⁄4 0.005). In a multivariate analysis, the risk of progression was lower in EGFR/FISH-positive patients (HR of EGFR/FISHþ vs. EGFR/ FISH , 0.57; P1⁄4 0.057) or patients experiencing grade 2 or more rash (HR for rash grade 2 or more vs. less than 2, 0.54; P 1⁄4 0.042), compared with EGFR/FISH-negative patients or those experiencing grade of less than 2 rash, respectively. When the combined criteria of EGFR/FISH and skin rash severity were analyzed, EGFR/FISH-negative patients with grade less than 2 rash had poorer clinical outcomes than patients with positive EGFR/FISH or grade 2 or more rash, apparent as a lower response rate (0.0% vs. 21.4%; P1⁄4 0.003) and a shorter median progression-free survival (1.13 months vs. 3.90 months; P 1⁄4 0.0002). Conclusions: EGFR/FISH and skin rash severitymay be used to identify which patients are likely to gain a benefit from EGFR-TKIs in this population. Clin Cancer Res; 18(6); 1760–8. 2012 AACR.