Evaluation of EGFR gene copy number as a predictive biomarker for the efficacy of cetuximab in combination with chemotherapy in the first-line treatment of recurrent and/or metastatic squamous cell carcinoma of the head and neck: EXTREME study

L. Licitra, R. Mesia, F. Rivera, É Remenár, R. Hitt, J. Erfán, S. Rottey, A. Kawecki, D. Zabolotnyy, M. Benasso, S. Störkel, S. Senger, C. Stroh, J. B. Vermorken

Research output: Contribution to journalArticle

Abstract

Background: The phase III EXTREME study demonstrated that combining cetuximab with platinum/5-fluorouracil (5-FU) significantly improved overall survival in the first-line treatment of patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) compared with platinum/5-FU alone. The aim of this investigation was to evaluate elevated tumor EGFR gene copy number as a predictive biomarker in EXTREME study patients. Patients and methods: Dual-color FISH was used to determine absolute and relative EGFR copy number. Models of differing stringencies were used to score and investigate whether increased copy number was predictive for the activity of cetuximab plus platinum/5-FU. Results: Tumors from 312 of 442 patients (71%) were evaluable by FISH and met the criteria for statistical analysis. A moderate increase in EGFR copy number was common, with high-level amplification of the gene occurring in a small fraction of tumors (~11%). Considering each of the models tested, no association of EGFR copy number with overall survival, progression-free survival or best overall response was found for patients treated with cetuximab plus platinum/5-FU. Conclusion: Tumor EGFR copy number is not a predictive biomarker for the efficacy of cetuximab plus platinum/5-FU as first-line therapy for patients with R/M SCCHN.

Original languageEnglish
Pages (from-to)1078-1087
Number of pages10
JournalAnnals of Oncology
Volume22
Issue number5
DOIs
Publication statusPublished - 2011

Fingerprint

erbB-1 Genes
Gene Dosage
Combination Drug Therapy
Platinum
Fluorouracil
Biomarkers
Neoplasms
Therapeutics
Survival
Gene Amplification
Disease-Free Survival
Cetuximab
Carcinoma, squamous cell of head and neck
Color

Keywords

  • Cetuximab
  • Copy number
  • EFGR
  • EXTREME
  • FISH
  • Platinum/5-fluorouracil

ASJC Scopus subject areas

  • Oncology
  • Hematology

Cite this

Evaluation of EGFR gene copy number as a predictive biomarker for the efficacy of cetuximab in combination with chemotherapy in the first-line treatment of recurrent and/or metastatic squamous cell carcinoma of the head and neck : EXTREME study. / Licitra, L.; Mesia, R.; Rivera, F.; Remenár, É; Hitt, R.; Erfán, J.; Rottey, S.; Kawecki, A.; Zabolotnyy, D.; Benasso, M.; Störkel, S.; Senger, S.; Stroh, C.; Vermorken, J. B.

In: Annals of Oncology, Vol. 22, No. 5, 2011, p. 1078-1087.

Research output: Contribution to journalArticle

Licitra, L. ; Mesia, R. ; Rivera, F. ; Remenár, É ; Hitt, R. ; Erfán, J. ; Rottey, S. ; Kawecki, A. ; Zabolotnyy, D. ; Benasso, M. ; Störkel, S. ; Senger, S. ; Stroh, C. ; Vermorken, J. B. / Evaluation of EGFR gene copy number as a predictive biomarker for the efficacy of cetuximab in combination with chemotherapy in the first-line treatment of recurrent and/or metastatic squamous cell carcinoma of the head and neck : EXTREME study. In: Annals of Oncology. 2011 ; Vol. 22, No. 5. pp. 1078-1087.
@article{ed190bcda123416da60bc67550c380cc,
title = "Evaluation of EGFR gene copy number as a predictive biomarker for the efficacy of cetuximab in combination with chemotherapy in the first-line treatment of recurrent and/or metastatic squamous cell carcinoma of the head and neck: EXTREME study",
abstract = "Background: The phase III EXTREME study demonstrated that combining cetuximab with platinum/5-fluorouracil (5-FU) significantly improved overall survival in the first-line treatment of patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) compared with platinum/5-FU alone. The aim of this investigation was to evaluate elevated tumor EGFR gene copy number as a predictive biomarker in EXTREME study patients. Patients and methods: Dual-color FISH was used to determine absolute and relative EGFR copy number. Models of differing stringencies were used to score and investigate whether increased copy number was predictive for the activity of cetuximab plus platinum/5-FU. Results: Tumors from 312 of 442 patients (71{\%}) were evaluable by FISH and met the criteria for statistical analysis. A moderate increase in EGFR copy number was common, with high-level amplification of the gene occurring in a small fraction of tumors (~11{\%}). Considering each of the models tested, no association of EGFR copy number with overall survival, progression-free survival or best overall response was found for patients treated with cetuximab plus platinum/5-FU. Conclusion: Tumor EGFR copy number is not a predictive biomarker for the efficacy of cetuximab plus platinum/5-FU as first-line therapy for patients with R/M SCCHN.",
keywords = "Cetuximab, Copy number, EFGR, EXTREME, FISH, Platinum/5-fluorouracil",
author = "L. Licitra and R. Mesia and F. Rivera and {\'E} Remen{\'a}r and R. Hitt and J. Erf{\'a}n and S. Rottey and A. Kawecki and D. Zabolotnyy and M. Benasso and S. St{\"o}rkel and S. Senger and C. Stroh and Vermorken, {J. B.}",
year = "2011",
doi = "10.1093/annonc/mdq588",
language = "English",
volume = "22",
pages = "1078--1087",
journal = "Annals of Oncology",
issn = "0923-7534",
publisher = "NLM (Medline)",
number = "5",

}

TY - JOUR

T1 - Evaluation of EGFR gene copy number as a predictive biomarker for the efficacy of cetuximab in combination with chemotherapy in the first-line treatment of recurrent and/or metastatic squamous cell carcinoma of the head and neck

T2 - EXTREME study

AU - Licitra, L.

AU - Mesia, R.

AU - Rivera, F.

AU - Remenár, É

AU - Hitt, R.

AU - Erfán, J.

AU - Rottey, S.

AU - Kawecki, A.

AU - Zabolotnyy, D.

AU - Benasso, M.

AU - Störkel, S.

AU - Senger, S.

AU - Stroh, C.

AU - Vermorken, J. B.

PY - 2011

Y1 - 2011

N2 - Background: The phase III EXTREME study demonstrated that combining cetuximab with platinum/5-fluorouracil (5-FU) significantly improved overall survival in the first-line treatment of patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) compared with platinum/5-FU alone. The aim of this investigation was to evaluate elevated tumor EGFR gene copy number as a predictive biomarker in EXTREME study patients. Patients and methods: Dual-color FISH was used to determine absolute and relative EGFR copy number. Models of differing stringencies were used to score and investigate whether increased copy number was predictive for the activity of cetuximab plus platinum/5-FU. Results: Tumors from 312 of 442 patients (71%) were evaluable by FISH and met the criteria for statistical analysis. A moderate increase in EGFR copy number was common, with high-level amplification of the gene occurring in a small fraction of tumors (~11%). Considering each of the models tested, no association of EGFR copy number with overall survival, progression-free survival or best overall response was found for patients treated with cetuximab plus platinum/5-FU. Conclusion: Tumor EGFR copy number is not a predictive biomarker for the efficacy of cetuximab plus platinum/5-FU as first-line therapy for patients with R/M SCCHN.

AB - Background: The phase III EXTREME study demonstrated that combining cetuximab with platinum/5-fluorouracil (5-FU) significantly improved overall survival in the first-line treatment of patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) compared with platinum/5-FU alone. The aim of this investigation was to evaluate elevated tumor EGFR gene copy number as a predictive biomarker in EXTREME study patients. Patients and methods: Dual-color FISH was used to determine absolute and relative EGFR copy number. Models of differing stringencies were used to score and investigate whether increased copy number was predictive for the activity of cetuximab plus platinum/5-FU. Results: Tumors from 312 of 442 patients (71%) were evaluable by FISH and met the criteria for statistical analysis. A moderate increase in EGFR copy number was common, with high-level amplification of the gene occurring in a small fraction of tumors (~11%). Considering each of the models tested, no association of EGFR copy number with overall survival, progression-free survival or best overall response was found for patients treated with cetuximab plus platinum/5-FU. Conclusion: Tumor EGFR copy number is not a predictive biomarker for the efficacy of cetuximab plus platinum/5-FU as first-line therapy for patients with R/M SCCHN.

KW - Cetuximab

KW - Copy number

KW - EFGR

KW - EXTREME

KW - FISH

KW - Platinum/5-fluorouracil

UR - http://www.scopus.com/inward/record.url?scp=79955496795&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79955496795&partnerID=8YFLogxK

U2 - 10.1093/annonc/mdq588

DO - 10.1093/annonc/mdq588

M3 - Article

C2 - 21048039

AN - SCOPUS:79955496795

VL - 22

SP - 1078

EP - 1087

JO - Annals of Oncology

JF - Annals of Oncology

SN - 0923-7534

IS - 5

ER -