Epidermal growth factor receptor gene copy number and clinical outcome of metastatic colorectal cancer treated with panitumumab

Andrea Sartore-Bianchi, Mauro Moroni, Silvio Veronese, Carlo Carnaghi, Emilio Bajetta, Gabriele Luppi, Alberto Sobrero, Carlo Barone, Stefano Cascinu, Giuseppe Colucci, Enrico Cortesi, Michele Nichelatti, Marcello Gambacorta, Salvatore Siena

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)3238-3245
Number of pages8
JournalJournal of Clinical Oncology
Volume25
Issue number22
DOIs
Publication statusPublished - Aug 1 2007

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erbB-1 Genes
Gene Dosage
Colorectal Neoplasms
Chromosomes, Human, Pair 7
Fluorescence In Situ Hybridization
Neoplasms
Epidermal Growth Factor Receptor
panitumumab
Disease-Free Survival
Cohort Studies
Monoclonal Antibodies

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Epidermal growth factor receptor gene copy number and clinical outcome of metastatic colorectal cancer treated with panitumumab. / Sartore-Bianchi, Andrea; Moroni, Mauro; Veronese, Silvio; Carnaghi, Carlo; Bajetta, Emilio; Luppi, Gabriele; Sobrero, Alberto; Barone, Carlo; Cascinu, Stefano; Colucci, Giuseppe; Cortesi, Enrico; Nichelatti, Michele; Gambacorta, Marcello; Siena, Salvatore.

In: Journal of Clinical Oncology, Vol. 25, No. 22, 01.08.2007, p. 3238-3245.

Research output: Contribution to journalArticle

Sartore-Bianchi, A, Moroni, M, Veronese, S, Carnaghi, C, Bajetta, E, Luppi, G, Sobrero, A, Barone, C, Cascinu, S, Colucci, G, Cortesi, E, Nichelatti, M, Gambacorta, M & Siena, S 2007, 'Epidermal growth factor receptor gene copy number and clinical outcome of metastatic colorectal cancer treated with panitumumab', Journal of Clinical Oncology, vol. 25, no. 22, pp. 3238-3245. https://doi.org/10.1200/JCO.2007.11.5956
Sartore-Bianchi, Andrea ; Moroni, Mauro ; Veronese, Silvio ; Carnaghi, Carlo ; Bajetta, Emilio ; Luppi, Gabriele ; Sobrero, Alberto ; Barone, Carlo ; Cascinu, Stefano ; Colucci, Giuseppe ; Cortesi, Enrico ; Nichelatti, Michele ; Gambacorta, Marcello ; Siena, Salvatore. / Epidermal growth factor receptor gene copy number and clinical outcome of metastatic colorectal cancer treated with panitumumab. In: Journal of Clinical Oncology. 2007 ; Vol. 25, No. 22. pp. 3238-3245.
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abstract = "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.",
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T1 - Epidermal growth factor receptor gene copy number and clinical outcome of metastatic colorectal cancer treated with panitumumab

AU - Sartore-Bianchi, Andrea

AU - Moroni, Mauro

AU - Veronese, Silvio

AU - Carnaghi, Carlo

AU - Bajetta, Emilio

AU - Luppi, Gabriele

AU - Sobrero, Alberto

AU - Barone, Carlo

AU - Cascinu, Stefano

AU - Colucci, Giuseppe

AU - Cortesi, Enrico

AU - Nichelatti, Michele

AU - Gambacorta, Marcello

AU - Siena, Salvatore

PY - 2007/8/1

Y1 - 2007/8/1

N2 - 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.

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.

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