PMID- 20824720
OWN - NLM
STAT- MEDLINE
DCOM- 20110317
LR  - 20221207
IS  - 0008-543X (Print)
IS  - 0008-543X (Linking)
VI  - 116
IP  - 24
DP  - 2010 Dec 15
TI  - Molecular predictors of outcome in a phase 3 study of gemcitabine and erlotinib 
      therapy in patients with advanced pancreatic cancer: National Cancer Institute of 
      Canada Clinical Trials Group Study PA.3.
PG  - 5599-607
LID - 10.1002/cncr.25393 [doi]
AB  - BACKGROUND: National Cancer Institute of Canada Clinical Trials Group PA.3 (NCIC 
      CTG PA.3) was a phase 3 study (n = 569) that demonstrated benefits for overall 
      survival and progression-free survival with the addition of the epidermal growth 
      factor receptor (EGFR) tyrosine kinase inhibitor (TKI) erlotinib to gemcitabine 
      in patients with advanced pancreatic carcinoma (APC). Mutation status of the 
      v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) and EGFR gene copy 
      number (GCN) were evaluated as predictive markers in 26% of patients who had 
      tumor samples available for analysis. METHODS: KRAS mutation status was evaluated 
      by direct sequencing of exon 2, and EGFR GCN was determined by fluorescence in 
      situ hybridization (FISH) analysis. The results were correlated with survival, 
      which was the primary endpoint of the trial. RESULTS: KRAS analysis was 
      successful in 117 patients, and EGFR FISH analysis was successful in 107 
      patients. KRAS mutations were identified in 92 patients (78.6%), and EGFR 
      amplification or high polysomy (FISH-positive results) was identified in 50 
      patients (46.7%). The hazard ratio of death between gemcitabine/erlotinib and 
      gemcitabine/placebo was 0.66 (95% confidence interval [CI], 0.28-1.57) for 
      patients with wild-type KRAS and 1.07 (95% CI, 0.68-1.66) for patients with 
      mutant KRAS (P value for interaction = .38), and the hazard ratio was 0.6 (95% 
      CI, 0.34-1.07) for FISH-negative patients and 0.90 (95% CI, 0.49-1.65) for 
      FISH-positive patients (P value for interaction = .32). CONCLUSIONS: In a 
      molecular subset analysis of patients from NCIC CTG PA.3, EGFR GCN and KRAS 
      mutation status were not identified as markers predictive of a survival benefit 
      from the combination of erlotinib with gemcitabine for the first-line treatment 
      of APC.
CI  - Copyright (c) 2010 American Cancer Society.
FAU - da Cunha Santos, Gilda
AU  - da Cunha Santos G
AD  - Department of Pathology, University Health Network, Ontario Cancer Institute, 
      Princess Margaret Hospital, Toronto, Ontario, Canada.
FAU - Dhani, Neesha
AU  - Dhani N
FAU - Tu, Dongsheng
AU  - Tu D
FAU - Chin, Kayu
AU  - Chin K
FAU - Ludkovski, Olga
AU  - Ludkovski O
FAU - Kamel-Reid, Suzanne
AU  - Kamel-Reid S
FAU - Squire, Jeremy
AU  - Squire J
FAU - Parulekar, Wendy
AU  - Parulekar W
FAU - Moore, Malcolm J
AU  - Moore MJ
FAU - Tsao, Ming Sound
AU  - Tsao MS
LA  - eng
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20100907
PL  - United States
TA  - Cancer
JT  - Cancer
JID - 0374236
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (KRAS protein, human)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Quinazolines)
RN  - 0W860991D6 (Deoxycytidine)
RN  - DA87705X9K (Erlotinib Hydrochloride)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 3.6.5.2 (Proto-Oncogene Proteins p21(ras))
RN  - EC 3.6.5.2 (ras Proteins)
RN  - 0 (Gemcitabine)
SB  - IM
MH  - Antineoplastic Combined Chemotherapy Protocols
MH  - Biomarkers, Tumor/*analysis
MH  - Canada
MH  - Deoxycytidine/administration & dosage/*analogs & derivatives
MH  - Disease-Free Survival
MH  - ErbB Receptors/antagonists & inhibitors/genetics
MH  - Erlotinib Hydrochloride
MH  - Gene Dosage
MH  - Humans
MH  - Mutation
MH  - Pancreatic Neoplasms/*drug therapy/mortality
MH  - Predictive Value of Tests
MH  - Proto-Oncogene Proteins/analysis/genetics
MH  - Proto-Oncogene Proteins p21(ras)
MH  - Quinazolines/*administration & dosage
MH  - Treatment Outcome
MH  - ras Proteins/analysis/genetics
MH  - Gemcitabine
EDAT- 2010/09/09 06:00
MHDA- 2011/03/18 06:00
CRDT- 2010/09/09 06:00
PHST- 2009/12/03 00:00 [received]
PHST- 2010/03/06 00:00 [revised]
PHST- 2010/03/23 00:00 [accepted]
PHST- 2010/09/09 06:00 [entrez]
PHST- 2010/09/09 06:00 [pubmed]
PHST- 2011/03/18 06:00 [medline]
AID - 10.1002/cncr.25393 [doi]
PST - ppublish
SO  - Cancer. 2010 Dec 15;116(24):5599-607. doi: 10.1002/cncr.25393. Epub 2010 Sep 7.