PMID- 19057271
OWN - NLM
STAT- MEDLINE
DCOM- 20090304
LR  - 20220316
IS  - 1556-1380 (Electronic)
IS  - 1556-0864 (Linking)
VI  - 3
IP  - 12
DP  - 2008 Dec
TI  - Epidermal growth factor receptor-related tumor markers and clinical outcomes with 
      erlotinib in non-small cell lung cancer: an analysis of patients from german 
      centers in the TRUST study.
PG  - 1446-53
LID - 10.1097/JTO.0b013e31818ddcaa [doi]
AB  - INTRODUCTION: Relationships between clinical outcomes and epidermal growth factor 
      receptor (EGFR)-related tumor markers were investigated in patients with advanced 
      non-small cell lung cancer. METHODS: Patients with stage IIIB/IV non-small cell 
      lung cancer (0-2 prior regimens) received erlotinib (150 mg PO per day). Response 
      and survival were evaluated, and tumor samples were assessed by 
      immunohistochemistry (EGFR, phosphorylated mitogen-activated protein kinase, and 
      phosphorylated AKT protein expression), fluorescence in situ hybridization (FISH; 
      EGFR gene copy number), and DNA sequencing (EGFR, KRAS gene mutations). RESULTS: 
      Among 311 patients, 8% had a complete/partial response; the disease control rate 
      was 66%. Median Overall survival (OS) was 6.1 months; 1-year survival rate was 
      27.2%. Two of 4 patients with EGFR mutations had tumor responses, versus 2/68 
      with wild-type EGFR (p = 0.014). Progression-free survival (PFS) (HR = 0.31) and 
      OS (HR = 0.33) were significantly prolonged in patients with EGFR mutations. 
      Response rate was significantly higher in patients with EGFR FISH-positive (17%) 
      than FISH-negative tumors (6%), and both PFS (HR = 0.58) and OS (HR = 0.63) 
      significantly favored patients with EGFR FISH-positive tumors; median OS was 8.6 
      months in the EGFR FISH-positive group. None of 17 patients with a KRAS mutation 
      had a tumor response, but the impact of KRAS mutation status on survival outcomes 
      was of borderline statistical significance. Neither phosphorylated 
      mitogen-activated protein kinase nor phosphorylated AKT immunohistochemistry 
      status had a significant effect on PFS and OS with erlotinib. CONCLUSIONS: The 
      presence of EGFR mutations and EGFR FISH-positive tumors may predispose patients 
      to achieving better outcomes on erlotinib, but may have a beneficial impact on 
      prognosis (irrespective of treatment). Prospective, placebo-controlled studies 
      are needed to determine the predictive value of the putative biomarkers.
FAU - Schneider, Claus-Peter
AU  - Schneider CP
AD  - Department of Oncological Pneumology, Central Clinic Bad Berka, Bad Berka, 
      Germany. cp.schneider.pne@zentralklinikbad-berka.de
FAU - Heigener, David
AU  - Heigener D
FAU - Schott-von-Romer, Kathrin
AU  - Schott-von-Romer K
FAU - Gutz, Sylvia
AU  - Gutz S
FAU - Laack, Eckart
AU  - Laack E
FAU - Digel, Werner
AU  - Digel W
FAU - Guschall, Wolf-Rudiger
AU  - Guschall WR
FAU - Franke, Andreas
AU  - Franke A
FAU - Bodenstein, Heinrich
AU  - Bodenstein H
FAU - Schmidtgen, Claudia
AU  - Schmidtgen C
FAU - Reck, Martin
AU  - Reck M
LA  - eng
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Thorac Oncol
JT  - Journal of thoracic oncology : official publication of the International 
      Association for the Study of Lung Cancer
JID - 101274235
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (KRAS protein, human)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Quinazolines)
RN  - DA87705X9K (Erlotinib Hydrochloride)
RN  - EC 2.7.10.1 (EGFR protein, human)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 3.6.5.2 (Proto-Oncogene Proteins p21(ras))
RN  - EC 3.6.5.2 (ras Proteins)
SB  - IM
MH  - Adenocarcinoma/drug therapy/genetics/metabolism
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Biomarkers, Tumor/genetics/*metabolism
MH  - Carcinoma, Non-Small-Cell Lung/drug therapy/genetics/*metabolism
MH  - Carcinoma, Squamous Cell/drug therapy/genetics/metabolism
MH  - Disease-Free Survival
MH  - ErbB Receptors/*genetics/*metabolism
MH  - Erlotinib Hydrochloride
MH  - Female
MH  - Gene Dosage
MH  - Germany
MH  - Humans
MH  - Immunoenzyme Techniques
MH  - In Situ Hybridization, Fluorescence
MH  - Lung Neoplasms/drug therapy/genetics/*metabolism
MH  - Male
MH  - Middle Aged
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - Mutation/genetics
MH  - Phosphorylation
MH  - Protein Kinase Inhibitors/*therapeutic use
MH  - Proto-Oncogene Proteins/genetics/metabolism
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Proto-Oncogene Proteins p21(ras)
MH  - Quinazolines/*therapeutic use
MH  - Survival Rate
MH  - Treatment Outcome
MH  - ras Proteins/genetics/metabolism
EDAT- 2008/12/06 09:00
MHDA- 2009/03/05 09:00
CRDT- 2008/12/06 09:00
PHST- 2008/12/06 09:00 [pubmed]
PHST- 2009/03/05 09:00 [medline]
PHST- 2008/12/06 09:00 [entrez]
AID - S1556-0864(15)32479-5 [pii]
AID - 10.1097/JTO.0b013e31818ddcaa [doi]
PST - ppublish
SO  - J Thorac Oncol. 2008 Dec;3(12):1446-53. doi: 10.1097/JTO.0b013e31818ddcaa.