PMID- 17664472
OWN - NLM
STAT- MEDLINE
DCOM- 20070913
LR  - 20181201
IS  - 1527-7755 (Electronic)
IS  - 0732-183X (Linking)
VI  - 25
IP  - 22
DP  - 2007 Aug 1
TI  - Epidermal growth factor receptor gene copy number and clinical outcome of 
      metastatic colorectal cancer treated with panitumumab.
PG  - 3238-45
AB  - PURPOSE: In a previous cohort study, we proposed that responsiveness of 
      metastatic colorectal cancer (mCRC) to anti-epidermal growth factor receptor 
      (EGFR) monoclonal antibodies has a genetic basis, being associated with increased 
      EGFR gene copy number (GCN) as measured by fluorescence in situ hybridization 
      (FISH) in individual tumors. The present study was aimed at assessing the 
      predictive role of EGFR GCN, in terms of clinical outcome, in patients treated 
      with panitumumab. PATIENTS AND METHODS: Patients with mCRC refractory to standard 
      therapies were a subset of patients from a phase III trial of panitumumab plus 
      best supportive care (BSC; n = 58) versus BSC alone (n = 34) who were selected on 
      the basis of availability of tumor samples adequate for FISH. RESULTS: In 
      patients treated with panitumumab, a mean EGFR GCN of less than 2.5/nucleus or 
      less than 40% of tumor cells displaying chromosome 7 polysomy within the tumor 
      predicted for shorter progression-free survival (PFS; P = .039 and P = .029, 
      respectively) and overall survival (P = .015 and P = .014, respectively). None of 
      the treated patients with mean EGFR GCN of less than 2.47/nucleus or less than 
      43% of tumor cells displaying chromosome 7 polysomy obtained objective response 
      compared with six of 20 and six of 19 patients with values greater than these 
      cutoff limits, respectively (P = .0009 and P = .0007, respectively). Evaluation 
      of BSC-treated patients showed no correlation between EGFR GCN or chromosome 7 
      polysomy status and PFS. CONCLUSION: In a larger and more homogeneous series than 
      in previous studies, present exploratory data suggest that mCRC patients with 
      tumors distinguishable by FISH analysis of EGFR as homogenously disomic or with 
      low chromosome 7 polysomy have a reduced likelihood of response to panitumumab.
FAU - Sartore-Bianchi, Andrea
AU  - Sartore-Bianchi A
AD  - Divisione Oncologia Falck, Ospedale Niguarda Ca' Granda, Piazza Ospedale Maggiore 
      3, 20162 Milan, Italy. salvatore.siena@ospedaleniguarda.it
FAU - Moroni, Mauro
AU  - Moroni M
FAU - Veronese, Silvio
AU  - Veronese S
FAU - Carnaghi, Carlo
AU  - Carnaghi C
FAU - Bajetta, Emilio
AU  - Bajetta E
FAU - Luppi, Gabriele
AU  - Luppi G
FAU - Sobrero, Alberto
AU  - Sobrero A
FAU - Barone, Carlo
AU  - Barone C
FAU - Cascinu, Stefano
AU  - Cascinu S
FAU - Colucci, Giuseppe
AU  - Colucci G
FAU - Cortesi, Enrico
AU  - Cortesi E
FAU - Nichelatti, Michele
AU  - Nichelatti M
FAU - Gambacorta, Marcello
AU  - Gambacorta M
FAU - Siena, Salvatore
AU  - Siena S
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
PL  - United States
TA  - J Clin Oncol
JT  - Journal of clinical oncology : official journal of the American Society of 
      Clinical Oncology
JID - 8309333
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antineoplastic Agents)
RN  - 6A901E312A (Panitumumab)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antibodies, Monoclonal/*therapeutic use
MH  - Antineoplastic Agents/*therapeutic use
MH  - Colorectal Neoplasms/*drug therapy/*genetics
MH  - Female
MH  - *Genes, erbB-1
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Italy
MH  - Logistic Models
MH  - Male
MH  - Middle Aged
MH  - Neoplasm Metastasis
MH  - Panitumumab
MH  - ROC Curve
MH  - Survival Rate
MH  - Treatment Outcome
EDAT- 2007/08/01 09:00
MHDA- 2007/09/14 09:00
CRDT- 2007/08/01 09:00
PHST- 2007/08/01 09:00 [pubmed]
PHST- 2007/09/14 09:00 [medline]
PHST- 2007/08/01 09:00 [entrez]
AID - 25/22/3238 [pii]
AID - 10.1200/JCO.2007.11.5956 [doi]
PST - ppublish
SO  - J Clin Oncol. 2007 Aug 1;25(22):3238-45. doi: 10.1200/JCO.2007.11.5956.