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

Authors
 Youngjoo Lee  ;  Hyo Sup Shim  ;  Moo Suk Park  ;  Joo-Hang Kim  ;  Sang-Jun Ha  ;  Se Hoon Kim  ;  Byoung Chul Cho 
Citation
 CLINICAL CANCER RESEARCH, Vol.18(6) : 1760-1768, 2012 
Journal Title
 CLINICAL CANCER RESEARCH 
ISSN
 1078-0432 
Issue Date
2012
MeSH
Aged ; Carcinoma, Squamous Cell/drug therapy ; Carcinoma, Squamous Cell/genetics* ; Carcinoma, Squamous Cell/mortality ; Exanthema/complications* ; Female ; Gene Dosage* ; Genes, erbB-1* ; Humans ; Lung Neoplasms/drug therapy ; Lung Neoplasms/genetics* ; Lung Neoplasms/mortality ; Male ; Middle Aged ; Protein Kinase Inhibitors/therapeutic use* ; Receptor, Epidermal Growth Factor/antagonists & inhibitors* ; Retreatment
Keywords
Aged ; Carcinoma, Squamous Cell/drug therapy ; Carcinoma, Squamous Cell/genetics* ; Carcinoma, Squamous Cell/mortality ; Exanthema/complications* ; Female ; Gene Dosage* ; Genes, erbB-1* ; Humans ; Lung Neoplasms/drug therapy ; Lung Neoplasms/genetics* ; Lung Neoplasms/mortality ; Male ; Middle Aged ; Protein Kinase Inhibitors/therapeutic use* ; Receptor, Epidermal Growth Factor/antagonists & inhibitors* ; Retreatment
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 cancer who received 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.
Files in This Item:
T201200549.pdf Download
DOI
22271877
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
Yonsei Authors
Kim, Se Hoon(김세훈) ORCID logo https://orcid.org/0000-0001-7516-7372
Kim, Joo Hang(김주항)
Park, Moo Suk(박무석) ORCID logo https://orcid.org/0000-0003-0820-7615
Shim, Hyo Sup(심효섭) ORCID logo https://orcid.org/0000-0002-5718-3624
Cho, Byoung Chul(조병철) ORCID logo https://orcid.org/0000-0002-5562-270X
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/90011
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