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.
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.


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.


CONCLUSIONS
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.
Division of Medical Oncology, Istituto Nazionale Tumori, Milan, Italy.
L
L
Licitra
Department of Medical Oncology, Catalan Institute of Oncology, L'Hospitalet de Llobregat, Barcelona, Spain.
R
R
Mesia
Medical Oncology Department, Marqués de Valdecilla University Hospital, Santander, Spain.
F
F
Rivera
Head and Neck Department, National Institute of Oncology, Budapest, Hungary.
É
É
Remenár
Medical Oncology Department, University Hospital 12 de Octubre, Madrid, Spain.
R
R
Hitt
Department of Oncoradiology, Jósa András County Hospital, Nyíregyháza, Hungary.
J
J
Erfán
Medical Oncology, Ghent University Hospital, Gent, Belgium.
S
S
Rottey
Head and Neck Cancer Department, Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Warsaw, Poland.
A
A
Kawecki
Institute of Otolaryngology, Academy of Medical Sciences of Ukraine, Kiev, Ukraine.
D
D
Zabolotnyy
Oncology Department, San Paolo Hospital, Savona, Italy.
M
M
Benasso
Institute of Pathology, HELIOS Hospital Wuppertal, Wuppertal, Germany.
S
S
Störkel
Global Biostatistics.
S
S
Senger
Oncology Research, Merck KGaA, Darmstadt, Germany.
C
C
Stroh
Department of Medical Oncology, Antwerp University Hospital, Edegem, Belgium. Electronic address: jan.b.vermorken@uza.be.
J B
JB
Vermorken
D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D000068818:Cetuximab; D066246:ErbB Receptors / Q000235:genetics*; D005472:Fluorouracil / Q000008:administration & dosage; D018628:Gene Dosage; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D006801:Humans; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D010984:Platinum / Q000008:administration & dosage; D016019:Survival Analysis; D016896:Treatment Outcome; D055815:Young Adult
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor; D010984:Platinum; D066246:ErbB Receptors; D000068818:Cetuximab; D005472:Fluorouracil