Cetuximab Shows Activity in Colorectal Cancer Patients With Tumors for Which FISH Analysis Does Not Detect an Increase in EGFR Gene Copy Number
EGFR (epidermal growth factor receptor) gene gain assessed by FISH (fluorescence in situ hybridization) has been shown to be predictive of response to EGFR-targeted therapies in patients with non–small cell lung cancer. The aim or our study was to relate the EGFR gene copy number to therapeutic results in patients with metastatic colorectal cancer (CRC) treated with a cetuximab-containing regimen.
Forty-seven patients with metastatic CRC treated with a cetuximab-containing regimen between August 2004 and September 2006 were included in our study. EGFR status was assessed by immunohistochemistry (IHC) and by FISH on fixed paraffin-embedded sections of tumor specimens.
By IHC (n = 47), 39 patients (83%) had EGFR-positive tumors. EGFR gene copy gain was detected in 8 (19.5%) of 41 tumors. Neither EGFR expression assessed by IHC nor EGFR gene copy gain assessed by FISH were statistically significantly correlated with objective response rate, disease control rate, progression-free survival, and overall survival. Of the 33 patients whose tumors were FISH negative, 8 patients (24.2%) had a partial response, and 10 (30.3%) had stable disease.
EGFR FISH analysis does not seem to be a sufficiently robust test for selecting candidate CRC patients for cetuximab therapy.
KeywordsEpidermal Growth Factor Receptor Cetuximab Epidermal Growth Factor Receptor Expression Epidermal Growth Factor Receptor Gene Epidermal Growth Factor Receptor Status
Supported by the Centre Hospitalier Universitaire de Nice (Contrat d’Incitation à la Recherche Clinique). We thank Laurence Bianchini, George Dettrakis, and Cecile Ortholan for editing the manuscript.
- 3.Jonker DJ, Karapetis CS, Moore M, et al. Randomized Phase III trial of cetuximab monotherapy plus best supportive care (BSC) versus BSC alone in patients with pretreated metastatic epidermal growth factor receptor (EGFR)-positive colorectal carcinoma: a trial of the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) and the Australasian Gastro-Intestinal Trials Group (AGITG). Proceedings of the American Association for Cancer Research Annual Meeting, 2007Google Scholar
- 14.Hamilton SR, Aaltonen LA. Pathology and Genetics of Tumours of Digestive System. Oxford: Oxford University Press, 2000Google Scholar
- 26.Kimura H, Sakai K, Arao T, et al. Antibody-dependent cellular cytotoxicity of cetuximab against tumor cells with wild-type or mutant epidermal growth factor receptor. Cancer Sci 2007;98:1275–80Google Scholar