Expression of epiregulin and amphiregulin and K-ras mutation status predict disease control in metastatic colorectal cancer patients treated with cetuximab.

@article{citeulike:2644588, abstract = {PURPOSE: The antiepidermal growth factor receptor (EGFR) antibody cetuximab shows activity in multiple epithelial tumor types; however, responses are seen in only a subset of patients. This study was conducted to identify markers that are associated with disease control in patients treated with cetuximab. PATIENTS AND METHODS: One hundred ten patients with metastatic colorectal cancer were enrolled onto a cetuximab monotherapy trial. Transcriptional profiling was conducted on RNA from mandatory pretreatment metastatic biopsies to identify genes whose expression correlates with best clinical responses. EGFR and K-ras mutation analyses and EGFR gene copy number analyses were performed on DNA from pretreatment biopsies. Results: Gene expression profiles showed that patients with tumors that express high levels of the EGFR ligands epiregulin and amphiregulin are more likely to have disease control with cetuximab (EREG, P = .000015; AREG, P = .000025). Additionally, patients whose tumors do not have K-ras mutations have a significantly higher disease control rate than patients with K-ras mutations (P = .0003). Furthermore, patients with tumors that have high expression of EREG or AREG also have significantly longer progression-free survival (PFS) than patients with low expression (EREG: P = .0002, hazard ratio [HR] = 0.47, and median PFS, 103.5 v 57 days, respectively; AREG: P < .0001, HR = 0.44, and median PFS, 115.5 v 57 days, respectively). CONCLUSION: Patients with tumors that have high gene expression levels of epiregulin and amphiregulin and patients with wild-type K-ras are more likely to have disease control on cetuximab treatment. The identified markers could be developed further to select patients for cetuximab therapy.}, address = {Bristol-Myers Squibb Co, Princeton, NJ 08543, USA. shirin.ford@bms.com}, author = {Khambata-Ford, S. and Garrett, C. R. and Meropol, N. J. and Basik, M. and Harbison, C. T. and Wu, S. and Wong, T. W. and Huang, X. and Takimoto, C. H. and Godwin, A. K. and Tan, B. R. and Krishnamurthi, S. S. and Burris, H. A. and Poplin, E. A. and Hidalgo, M. and Baselga, J. and Clark, E. A. and Mauro, D. J. }, citeulike-article-id = {2644588}, doi = {10.1200/JCO.2006.10.5437}, issn = {1527-7755}, journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology}, keywords = {classification, colon\_cancer, gene\_expression, therapy}, month = {August}, number = {22}, pages = {3230--3237}, posted-at = {2008-04-09 13:55:11}, priority = {4}, title = {Expression of epiregulin and amphiregulin and K-ras mutation status predict disease control in metastatic colorectal cancer patients treated with cetuximab.}, url = {http://dx.doi.org/10.1200/JCO.2006.10.5437}, volume = {25}, year = {2007} }

TY - JOUR ID - citeulike:2644588 L3 - citeulike-article-id:2644588 TI - Expression of epiregulin and amphiregulin and K-ras mutation status predict disease control in metastatic colorectal cancer patients treated with cetuximab. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology VL - 25 IS - 22 SP - 3230 EP - 3237 AD - Bristol-Myers Squibb Co, Princeton, NJ 08543, USA. shirin.ford@bms.com SN - 1527-7755 N2 - PURPOSE: The antiepidermal growth factor receptor (EGFR) antibody cetuximab shows activity in multiple epithelial tumor types; however, responses are seen in only a subset of patients. This study was conducted to identify markers that are associated with disease control in patients treated with cetuximab. PATIENTS AND METHODS: One hundred ten patients with metastatic colorectal cancer were enrolled onto a cetuximab monotherapy trial. Transcriptional profiling was conducted on RNA from mandatory pretreatment metastatic biopsies to identify genes whose expression correlates with best clinical responses. EGFR and K-ras mutation analyses and EGFR gene copy number analyses were performed on DNA from pretreatment biopsies. Results: Gene expression profiles showed that patients with tumors that express high levels of the EGFR ligands epiregulin and amphiregulin are more likely to have disease control with cetuximab (EREG, P = .000015; AREG, P = .000025). Additionally, patients whose tumors do not have K-ras mutations have a significantly higher disease control rate than patients with K-ras mutations (P = .0003). Furthermore, patients with tumors that have high expression of EREG or AREG also have significantly longer progression-free survival (PFS) than patients with low expression (EREG: P = .0002, hazard ratio [HR] = 0.47, and median PFS, 103.5 v 57 days, respectively; AREG: P < .0001, HR = 0.44, and median PFS, 115.5 v 57 days, respectively). CONCLUSION: Patients with tumors that have high gene expression levels of epiregulin and amphiregulin and patients with wild-type K-ras are more likely to have disease control on cetuximab treatment. The identified markers could be developed further to select patients for cetuximab therapy. KW - classification KW - colon_cancer KW - gene_expression KW - therapy AU - Khambata-Ford, S AU - Garrett, CR AU - Meropol, NJ AU - Basik, M AU - Harbison, CT AU - Wu, S AU - Wong, TW AU - Huang, X AU - Takimoto, CH AU - Godwin, AK AU - Tan, BR AU - Krishnamurthi, SS AU - Burris, HA AU - Poplin, EA AU - Hidalgo, M AU - Baselga, J AU - Clark, EA AU - Mauro, DJ PY - 2007/08/01/ UR - http://dx.doi.org/10.1200/JCO.2006.10.5437 ER -