PMID- 18829515
OWN - NLM
STAT- MEDLINE
DCOM- 20081126
LR  - 20220416
IS  - 1078-0432 (Print)
IS  - 1078-0432 (Electronic)
IS  - 1078-0432 (Linking)
VI  - 14
IP  - 19
DP  - 2008 Oct 1
TI  - Fluorescence in situ hybridization subgroup analysis of TRIBUTE, a phase III 
      trial of erlotinib plus carboplatin and paclitaxel in non-small cell lung cancer.
PG  - 6317-23
LID - 10.1158/1078-0432.CCR-08-0539 [doi]
AB  - PURPOSE: TRIBUTE was a phase III trial evaluating the addition of erlotinib to 
      carboplatin and paclitaxel as a first-line treatment for advanced non-small cell 
      lung cancer that did not meet its primary end point of improving overall 
      survival. Here, we assess the value of using epidermal growth factor receptor 
      (EGFR) gene copy number in tumor biopsy samples, as determined by fluorescence in 
      situ hybridization (FISH), as a predictor of treatment outcome. METHODS: EGFR 
      FISH analysis was done using LSI EGFR SpectrumOrange/CEP7 SpectrumGreen probe. 
      RESULTS: Of 275 samples, 245 (89.1%) were successfully analyzed by FISH. One 
      hundred (40.8%) of patients were EGFR FISH(+). Median overall survival was not 
      different between FISH(+) and FISH(-) patients in either the 
      chemotherapy+erlotinib arm or the chemotherapy+placebo arm. In FISH(+) patients, 
      median time to progression (TTP) was 6.3 months in the erlotinib arm versus 5.8 
      months in the placebo arm (hazard ratio, 0.59; 95% confidence interval, 
      0.35-0.99; P = 0.0430); in FISH(-) patients, median TTP was 4.6 months versus 6.0 
      months (hazard ratio, 1.42; 95% confidence interval, 0.95-2.14; P = 0.0895; 
      treatment interaction test, P = 0.007). After 6 months of treatment, a notable 
      separation of the TTP curves in favor of erlotinib emerged. Objective response 
      rates were 11.6% versus 29.8% in FISH(+) patients (chemotherapy+erlotinib arm 
      versus chemotherapy+placebo arm; P = 0.0495) and 21.8% versus 25.4%, 
      respectively, for FISH(-) patients (P = 0.6954). CONCLUSIONS: EGFR gene copy 
      number by FISH did not predict survival benefit. However, among EGFR FISH(+) 
      patients, TTP was longer in patients who received erlotinib and continued to 
      receive it after completing first-line therapy.
FAU - Hirsch, Fred R
AU  - Hirsch FR
AD  - University of Colorado Cancer Center, Aurora, CO 80045, USA. 
      Fred.Hirsch@UCHSC.edu
FAU - Varella-Garcia, Marileila
AU  - Varella-Garcia M
FAU - Dziadziuszko, Rafal
AU  - Dziadziuszko R
FAU - Xiao, Yun
AU  - Xiao Y
FAU - Gajapathy, Sujatha
AU  - Gajapathy S
FAU - Skokan, Margaret
AU  - Skokan M
FAU - Lin, Ming
AU  - Lin M
FAU - O'Neill, Vincent
AU  - O'Neill V
FAU - Bunn, Paul A Jr
AU  - Bunn PA Jr
LA  - eng
GR  - P50 CA058187/CA/NCI NIH HHS/United States
GR  - P01 CA 58187/CA/NCI NIH HHS/United States
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Clin Cancer Res
JT  - Clinical cancer research : an official journal of the American Association for 
      Cancer Research
JID - 9502500
RN  - 0 (Quinazolines)
RN  - BG3F62OND5 (Carboplatin)
RN  - DA87705X9K (Erlotinib Hydrochloride)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - P88XT4IS4D (Paclitaxel)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use
MH  - Carboplatin/*administration & dosage
MH  - Carcinoma, Non-Small-Cell Lung/*drug therapy/*genetics
MH  - ErbB Receptors/*genetics/metabolism
MH  - Erlotinib Hydrochloride
MH  - Female
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - In Situ Hybridization, Fluorescence/*methods
MH  - Lung Neoplasms/*drug therapy/*genetics
MH  - Male
MH  - Middle Aged
MH  - Paclitaxel/*administration & dosage
MH  - Quinazolines/*administration & dosage
PMC - PMC3368373
MID - NIHMS375690
EDAT- 2008/10/03 09:00
MHDA- 2008/12/17 09:00
PMCR- 2012/06/06
CRDT- 2008/10/03 09:00
PHST- 2008/10/03 09:00 [pubmed]
PHST- 2008/12/17 09:00 [medline]
PHST- 2008/10/03 09:00 [entrez]
PHST- 2012/06/06 00:00 [pmc-release]
AID - 14/19/6317 [pii]
AID - 10.1158/1078-0432.CCR-08-0539 [doi]
PST - ppublish
SO  - Clin Cancer Res. 2008 Oct 1;14(19):6317-23. doi: 10.1158/1078-0432.CCR-08-0539.