PMID- 29158193
OWN - NLM
STAT- MEDLINE
DCOM- 20190403
LR  - 20200516
IS  - 1556-1380 (Electronic)
IS  - 1556-0864 (Print)
IS  - 1556-0864 (Linking)
VI  - 13
IP  - 2
DP  - 2018 Feb
TI  - EGFR Gene Copy Number by FISH May Predict Outcome of Necitumumab in Squamous Lung 
      Carcinomas: Analysis from the SQUIRE Study.
PG  - 228-236
LID - S1556-0864(17)33006-X [pii]
LID - 10.1016/j.jtho.2017.11.109 [doi]
AB  - INTRODUCTION: Necitumumab is a monoclonal antibody targeting EGFR. In the SQUIRE 
      trial, the addition of necitumumab to chemotherapy for squamous cell lung cancer 
      significantly improved overall survival (OS) (hazard ratio [HR] = 0.84); in a 
      post hoc analysis, EGFR copy number gain determined by fluorescence in situ 
      hybridization (FISH) showed a trend toward improved OS (HR = 0.70) and 
      progression-free survival (PFS) (HR = 0.71) with the addition of necitumumab. We 
      present the analysis of granular EGFR FISH data from SQUIRE to examine the 
      potential predictive role of high polysomy and gene amplification, as both were 
      included in the FISH-positive category. METHODS: Available specimens from SQUIRE 
      underwent FISH analysis in a central laboratory, and each sample was evaluated by 
      using the Colorado EGFR scoring criteria. The correlation of granular FISH 
      parameters with clinical outcomes was assessed. RESULTS: Samples were available 
      for 557 of 1093 patients; 208 patients (37.3%) were FISH-positive, including 167 
      (30.0%) with high polysomy and 41 (7.4%) with gene amplification. In patients 
      with high polysomy, the addition of necitumumab resulted in a statistically 
      significant increase in PFS (6.08 versus 5.13 months [p = 0.044]) and 
      nonstatistically significant increase in OS (12.6 versus 9.5 months [p = 0.133]); 
      among patients with gene amplification, the addition of necitumumab did not 
      significantly improve PFS (7.4 versus 5.6 months; [p = 0.334]) but did improve OS 
      (14.8 versus 7.6 months; [p = 0.033]). CONCLUSIONS: EGFR copy number gain by FISH 
      might have a role as a predictive biomarker for necitumumab in squamous cell lung 
      cancer. In our opinion, these data encourage further studies to prospectively 
      evaluate this potential biomarker.
CI  - Copyright (c) 2018 International Association for the Study of Lung Cancer. 
      Published by Elsevier Inc. All rights reserved.
FAU - Genova, Carlo
AU  - Genova C
AD  - Lung Cancer Unit, San Martino Hospital, Genoa, Italy; Department of Internal 
      Medicine, School of Medicine, University of Genoa, Genoa, Italy.
FAU - Socinski, Mark A
AU  - Socinski MA
AD  - Florida Hospital Cancer Institute, Orlando, Florida.
FAU - Hozak, Rebecca R
AU  - Hozak RR
AD  - Eli Lilly and Company, Indianapolis, Indiana.
FAU - Mi, Gu
AU  - Mi G
AD  - Eli Lilly and Company, Indianapolis, Indiana.
FAU - Kurek, Raffael
AU  - Kurek R
AD  - Lilly Deutschland GMBH, Bad Homburg vor der Hohe, Germany.
FAU - Shahidi, Javad
AU  - Shahidi J
AD  - Eli Lilly and Company, Bridgewater, New Jersey.
FAU - Paz-Ares, Luis
AU  - Paz-Ares L
AD  - University Hospital Virgen del Rocio, Seville, Spain.
FAU - Thatcher, Nick
AU  - Thatcher N
AD  - The Christie Hospital, Manchester, United Kingdom.
FAU - Rivard, Christopher J
AU  - Rivard CJ
AD  - Division of Medical Oncology, Department of Medicine, Anschutz Medical Campus, 
      University of Colorado, Aurora, Colorado.
FAU - Varella-Garcia, Marileila
AU  - Varella-Garcia M
AD  - Division of Medical Oncology, Department of Medicine, Anschutz Medical Campus, 
      University of Colorado, Aurora, Colorado.
FAU - Hirsch, Fred R
AU  - Hirsch FR
AD  - Division of Medical Oncology, Department of Medicine, Anschutz Medical Campus, 
      University of Colorado, Aurora, Colorado. Electronic address: 
      Fred.Hirsch@ucdenver.edu.
LA  - eng
GR  - P30 CA046934/CA/NCI NIH HHS/United States
PT  - Journal Article
DEP - 20171120
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 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Antineoplastic Agents, Immunological)
RN  - 2BT4C47RUI (necitumumab)
SB  - IM
MH  - Antibodies, Monoclonal/pharmacology/*therapeutic use
MH  - Antibodies, Monoclonal, Humanized
MH  - Antineoplastic Agents, Immunological/pharmacology/*therapeutic use
MH  - Carcinoma, Squamous Cell/*drug therapy/*genetics/pathology
MH  - Female
MH  - Gene Dosage/*genetics
MH  - Humans
MH  - In Situ Hybridization, Fluorescence/*methods
MH  - Lung Neoplasms/*drug therapy/*genetics/pathology
MH  - Male
MH  - Treatment Outcome
PMC - PMC6233716
MID - NIHMS1504198
OTO - NOTNLM
OT  - EGFR
OT  - FISH
OT  - Non-small cell lung cancer
OT  - biomarker
OT  - necitumumab
EDAT- 2017/11/22 06:00
MHDA- 2019/04/04 06:00
PMCR- 2019/02/01
CRDT- 2017/11/22 06:00
PHST- 2017/08/12 00:00 [received]
PHST- 2017/10/09 00:00 [revised]
PHST- 2017/11/08 00:00 [accepted]
PHST- 2017/11/22 06:00 [pubmed]
PHST- 2019/04/04 06:00 [medline]
PHST- 2017/11/22 06:00 [entrez]
PHST- 2019/02/01 00:00 [pmc-release]
AID - S1556-0864(17)33006-X [pii]
AID - 10.1016/j.jtho.2017.11.109 [doi]
PST - ppublish
SO  - J Thorac Oncol. 2018 Feb;13(2):228-236. doi: 10.1016/j.jtho.2017.11.109. Epub 
      2017 Nov 20.