High EGFR gene copy number and skin rash as predictive markers for EGFR tyrosine kinase inhibitors in patients with advanced squamous cell lung carcinoma

Youngjoo Lee, Hyo Sup Shim, Moo Suk Park, Joo Hang Kim, Sang Jun Ha, Se Hoon Kim, Byoung Chul Cho

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

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 in 71 patients with advanced squamous cell lung cancerwhoreceived gefitinib or 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/FISH + vs. EGFR/FISH -, 26.3% vs. 2.0%; P = 0.005). In a multivariate analysis, the risk of progression was lower in EGFR/FISH-positive patients (HR of EGFR/FISH + vs. EGFR/ FISH -, 0.57; P = 0.057) or patients experiencing grade 2 or more rash (HR for rash grade 2 or more vs. less than 2, 0.54; P = 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%; P = 0.003) and a shorter median progression-free survival (1.13 months vs. 3.90 months; P = 0.0002). Conclusions: EGFR/FISH and skin rash severity may be used to identify which patients are likely to gain a benefit from EGFR-TKIs in this population.

Original languageEnglish
Pages (from-to)1760-1768
Number of pages9
JournalClinical Cancer Research
Volume18
Issue number6
DOIs
Publication statusPublished - 2012 Mar 15

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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