Primary tumor site is a useful predictor of cetuximab efficacy in the third-line or salvage treatment of KRAS wild-type (exon 2 non-mutant) metastatic colorectal cancer: a nationwide cohort study

go back to reference Karapetis CS, Khambata-Ford S, Jonker DJ, O'Callaghan CJ, Tu D, Tebbutt NC, et al. K-ras mutations and benefit from cetuximab in advanced colorectal cancer. N Engl J Med. 2008;359(17):1757–65.CrossRefPubMed Karapetis CS, Khambata-Ford S, Jonker DJ, O'Callaghan CJ, Tu D, Tebbutt NC, et al. K-ras mutations and benefit from cetuximab in advanced colorectal cancer. N Engl J Med. 2008;359(17):1757–65.CrossRefPubMed

go back to reference Van Cutsem E, Kohne CH, Lang I, Folprecht G, Nowacki MP, Cascinu S, et al. Cetuximab plus irinotecan, fluorouracil, and leucovorin as first-line treatment for metastatic colorectal cancer: updated analysis of overall survival according to tumor KRAS and BRAF mutation status. J Clin Oncol. 2011;29(15):2011–9.CrossRefPubMed Van Cutsem E, Kohne CH, Lang I, Folprecht G, Nowacki MP, Cascinu S, et al. Cetuximab plus irinotecan, fluorouracil, and leucovorin as first-line treatment for metastatic colorectal cancer: updated analysis of overall survival according to tumor KRAS and BRAF mutation status. J Clin Oncol. 2011;29(15):2011–9.CrossRefPubMed

go back to reference Van Cutsem E, Lenz HJ, Kohne CH, Heinemann V, Tejpar S, Melezinek I, et al. Fluorouracil, Leucovorin, and Irinotecan Plus Cetuximab Treatment and RAS Mutations in Colorectal Cancer. J Clin Oncol. 2015;33(7):692–700.CrossRefPubMed Van Cutsem E, Lenz HJ, Kohne CH, Heinemann V, Tejpar S, Melezinek I, et al. Fluorouracil, Leucovorin, and Irinotecan Plus Cetuximab Treatment and RAS Mutations in Colorectal Cancer. J Clin Oncol. 2015;33(7):692–700.CrossRefPubMed

go back to reference Amado RG, Wolf M, Peeters M, Van Cutsem E, Siena S, Freeman DJ, et al. Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. J Clin Oncol. 2008;26(10):1626–34.CrossRefPubMed Amado RG, Wolf M, Peeters M, Van Cutsem E, Siena S, Freeman DJ, et al. Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. J Clin Oncol. 2008;26(10):1626–34.CrossRefPubMed

go back to reference Douillard JY, Oliner KS, Siena S, Tabernero J, Burkes R, Barugel M, et al. Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer. N Engl J Med. 2013;369(11):1023–34.CrossRefPubMed Douillard JY, Oliner KS, Siena S, Tabernero J, Burkes R, Barugel M, et al. Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer. N Engl J Med. 2013;369(11):1023–34.CrossRefPubMed

go back to reference Heinemann V, von Weikersthal LF, Decker T, Kiani A, Vehling-Kaiser U, Al-Batran SE, et al. FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer (FIRE-3): a randomised, open-label, phase 3 trial. Lancet Oncol. 2014;15(10):1065–75.CrossRefPubMed Heinemann V, von Weikersthal LF, Decker T, Kiani A, Vehling-Kaiser U, Al-Batran SE, et al. FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer (FIRE-3): a randomised, open-label, phase 3 trial. Lancet Oncol. 2014;15(10):1065–75.CrossRefPubMed

go back to reference Jacobs B, De Roock W, Piessevaux H, Van Oirbeek R, Biesmans B, De Schutter J, et al. Amphiregulin and epiregulin mRNA expression in primary tumors predicts outcome in metastatic colorectal cancer treated with cetuximab. J Clin Oncol. 2009;27(30):5068–74.CrossRefPubMed Jacobs B, De Roock W, Piessevaux H, Van Oirbeek R, Biesmans B, De Schutter J, et al. Amphiregulin and epiregulin mRNA expression in primary tumors predicts outcome in metastatic colorectal cancer treated with cetuximab. J Clin Oncol. 2009;27(30):5068–74.CrossRefPubMed

go back to reference Khambata-Ford S, Garrett CR, Meropol NJ, Basik M, Harbison CT, Wu S, et al. Expression of epiregulin and amphiregulin and K-ras mutation status predict disease control in metastatic colorectal cancer patients treated with cetuximab. J Clin Oncol. 2007;25(22):3230–7.CrossRefPubMed Khambata-Ford S, Garrett CR, Meropol NJ, Basik M, Harbison CT, Wu S, et al. Expression of epiregulin and amphiregulin and K-ras mutation status predict disease control in metastatic colorectal cancer patients treated with cetuximab. J Clin Oncol. 2007;25(22):3230–7.CrossRefPubMed

go back to reference De Roock W, Claes B, Bernasconi D, De Schutter J, Biesmans B, Fountzilas G, et al. Effects of KRAS, BRAF, NRAS, and PIK3CA mutations on the efficacy of cetuximab plus chemotherapy in chemotherapy-refractory metastatic colorectal cancer: a retrospective consortium analysis. Lancet Oncol. 2010;11(8):753–62.CrossRefPubMed De Roock W, Claes B, Bernasconi D, De Schutter J, Biesmans B, Fountzilas G, et al. Effects of KRAS, BRAF, NRAS, and PIK3CA mutations on the efficacy of cetuximab plus chemotherapy in chemotherapy-refractory metastatic colorectal cancer: a retrospective consortium analysis. Lancet Oncol. 2010;11(8):753–62.CrossRefPubMed

go back to reference Schwartzberg LS, Rivera F, Karthaus M, Fasola G, Canon JL, Hecht JR, et al. PEAK: a randomized, multicenter phase II study of panitumumab plus modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) or bevacizumab plus mFOLFOX6 in patients with previously untreated, unresectable, wild-type KRAS exon 2 metastatic colorectal cancer. J Clin Oncol. 2014;32(21):2240–7.CrossRefPubMed Schwartzberg LS, Rivera F, Karthaus M, Fasola G, Canon JL, Hecht JR, et al. PEAK: a randomized, multicenter phase II study of panitumumab plus modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) or bevacizumab plus mFOLFOX6 in patients with previously untreated, unresectable, wild-type KRAS exon 2 metastatic colorectal cancer. J Clin Oncol. 2014;32(21):2240–7.CrossRefPubMed

go back to reference Peeters M, Oliner KS, Parker A, Siena S, Van Cutsem E, Huang J, et al. Massively parallel tumor multigene sequencing to evaluate response to panitumumab in a randomized phase III study of metastatic colorectal cancer. Clin Cancer Res. 2013;19(7):1902–12.CrossRefPubMed Peeters M, Oliner KS, Parker A, Siena S, Van Cutsem E, Huang J, et al. Massively parallel tumor multigene sequencing to evaluate response to panitumumab in a randomized phase III study of metastatic colorectal cancer. Clin Cancer Res. 2013;19(7):1902–12.CrossRefPubMed

go back to reference Di Nicolantonio F, Martini M, Molinari F, Sartore-Bianchi A, Arena S, Saletti P, et al. Wild-type BRAF is required for response to panitumumab or cetuximab in metastatic colorectal cancer. J Clin Oncol. 2008;26(35):5705–12.CrossRefPubMed Di Nicolantonio F, Martini M, Molinari F, Sartore-Bianchi A, Arena S, Saletti P, et al. Wild-type BRAF is required for response to panitumumab or cetuximab in metastatic colorectal cancer. J Clin Oncol. 2008;26(35):5705–12.CrossRefPubMed

go back to reference Laurent-Puig P, Cayre A, Manceau G, Buc E, Bachet JB, Lecomte T, et al. Analysis of PTEN, BRAF, and EGFR status in determining benefit from cetuximab therapy in wild-type KRAS metastatic colon cancer. J Clin Oncol. 2009;27(35):5924–30.CrossRefPubMed Laurent-Puig P, Cayre A, Manceau G, Buc E, Bachet JB, Lecomte T, et al. Analysis of PTEN, BRAF, and EGFR status in determining benefit from cetuximab therapy in wild-type KRAS metastatic colon cancer. J Clin Oncol. 2009;27(35):5924–30.CrossRefPubMed

go back to reference Valtorta E, Misale S, Sartore-Bianchi A, Nagtegaal ID, Paraf F, Lauricella C, et al. KRAS gene amplification in colorectal cancer and impact on response to EGFR-targeted therapy. Int J Cancer. 2013;133(5):1259–65.CrossRefPubMed Valtorta E, Misale S, Sartore-Bianchi A, Nagtegaal ID, Paraf F, Lauricella C, et al. KRAS gene amplification in colorectal cancer and impact on response to EGFR-targeted therapy. Int J Cancer. 2013;133(5):1259–65.CrossRefPubMed

go back to reference Yonesaka K, Zejnullahu K, Okamoto I, Satoh T, Cappuzzo F, Souglakos J, et al. Activation of ERBB2 signaling causes resistance to the EGFR-directed therapeutic antibody cetuximab. Sci Transl Med. 2011;3(99):99ra86.CrossRefPubMedPubMedCentral Yonesaka K, Zejnullahu K, Okamoto I, Satoh T, Cappuzzo F, Souglakos J, et al. Activation of ERBB2 signaling causes resistance to the EGFR-directed therapeutic antibody cetuximab. Sci Transl Med. 2011;3(99):99ra86.CrossRefPubMedPubMedCentral

go back to reference Bardelli A, Corso S, Bertotti A, Hobor S, Valtorta E, Siravegna G, et al. Amplification of the MET receptor drives resistance to anti-EGFR therapies in colorectal cancer. Cancer Discov. 2013;3(6):658–73.CrossRefPubMedPubMedCentral Bardelli A, Corso S, Bertotti A, Hobor S, Valtorta E, Siravegna G, et al. Amplification of the MET receptor drives resistance to anti-EGFR therapies in colorectal cancer. Cancer Discov. 2013;3(6):658–73.CrossRefPubMedPubMedCentral

go back to reference Karapetis CS, Jonker D, Daneshmand M, Hanson JE, O'Callaghan CJ, Marginean C, et al. PIK3CA, BRAF, and PTEN status and benefit from cetuximab in the treatment of advanced colorectal cancer--results from NCIC CTG/AGITG CO.17. Clin Cancer Res. 2014;20(3):744–53.CrossRefPubMed Karapetis CS, Jonker D, Daneshmand M, Hanson JE, O'Callaghan CJ, Marginean C, et al. PIK3CA, BRAF, and PTEN status and benefit from cetuximab in the treatment of advanced colorectal cancer--results from NCIC CTG/AGITG CO.17. Clin Cancer Res. 2014;20(3):744–53.CrossRefPubMed

go back to reference Missiaglia E, Jacobs B, D'Ario G, Di Narzo AF, Soneson C, Budinska E, et al. Distal and proximal colon cancers differ in terms of molecular, pathological, and clinical features. Ann Oncol. 2014;25(10):1995–2001.CrossRefPubMed Missiaglia E, Jacobs B, D'Ario G, Di Narzo AF, Soneson C, Budinska E, et al. Distal and proximal colon cancers differ in terms of molecular, pathological, and clinical features. Ann Oncol. 2014;25(10):1995–2001.CrossRefPubMed

go back to reference Iacopetta B. Are there two sides to colorectal cancer? Int J Cancer. 2002;101(5):403–8.CrossRefPubMed Iacopetta B. Are there two sides to colorectal cancer? Int J Cancer. 2002;101(5):403–8.CrossRefPubMed

go back to reference Azzoni C, Bottarelli L, Campanini N, Di Cola G, Bader G, Mazzeo A, et al. Distinct molecular patterns based on proximal and distal sporadic colorectal cancer: arguments for different mechanisms in the tumorigenesis. Int J Color Dis. 2007;22(2):115–26.CrossRef Azzoni C, Bottarelli L, Campanini N, Di Cola G, Bader G, Mazzeo A, et al. Distinct molecular patterns based on proximal and distal sporadic colorectal cancer: arguments for different mechanisms in the tumorigenesis. Int J Color Dis. 2007;22(2):115–26.CrossRef

go back to reference von Einem JC, Heinemann V, von Weikersthal LF, Vehling-Kaiser U, Stauch M, Hass HG, et al. Left-sided primary tumors are associated with favorable prognosis in patients with KRAS codon 12/13 wild-type metastatic colorectal cancer treated with cetuximab plus chemotherapy: an analysis of the AIO KRK-0104 trial. J Cancer Res Clin Oncol. 2014;140(9):1607–14.CrossRef von Einem JC, Heinemann V, von Weikersthal LF, Vehling-Kaiser U, Stauch M, Hass HG, et al. Left-sided primary tumors are associated with favorable prognosis in patients with KRAS codon 12/13 wild-type metastatic colorectal cancer treated with cetuximab plus chemotherapy: an analysis of the AIO KRK-0104 trial. J Cancer Res Clin Oncol. 2014;140(9):1607–14.CrossRef

go back to reference Brule SY, Jonker DJ, Karapetis CS, O'Callaghan CJ, Moore MJ, Wong R, et al. Location of colon cancer (right-sided versus left-sided) as a prognostic factor and a predictor of benefit from cetuximab in NCIC CO.17. Eur J Cancer. 2015;51(11):1405–14.CrossRefPubMed Brule SY, Jonker DJ, Karapetis CS, O'Callaghan CJ, Moore MJ, Wong R, et al. Location of colon cancer (right-sided versus left-sided) as a prognostic factor and a predictor of benefit from cetuximab in NCIC CO.17. Eur J Cancer. 2015;51(11):1405–14.CrossRefPubMed

go back to reference Heinemann V, von Weikersthal LF, Decker T, Kiani A, Vehling-Kaiser U, Al-Batran SE, et al. Gender and tumor location as predictors for efficacy: Influence on endpoints in first-line treatment with FOLFIRI in combination with cetuximab or bevacizumab in the AIO KRK 0306 (FIRE3) trial. J Clin Oncol 32:5s, 2014 (suppl; abstr 3600). 2014 Heinemann V, von Weikersthal LF, Decker T, Kiani A, Vehling-Kaiser U, Al-Batran SE, et al. Gender and tumor location as predictors for efficacy: Influence on endpoints in first-line treatment with FOLFIRI in combination with cetuximab or bevacizumab in the AIO KRK 0306 (FIRE3) trial. J Clin Oncol 32:5s, 2014 (suppl; abstr 3600). 2014

go back to reference National Health Insurance in Taiwan 2010. <http://www.nhi.gov.tw/webdata/webdata.aspx?menu=20&menu_id=710&WD_ID=812&webdata_id=2919> [Accessed 1 Apr 2012]. National Health Insurance in Taiwan 2010. <http://​www.​nhi.​gov.​tw/​webdata/​webdata.​aspx?​menu=​20&​menu_​id=​710&​WD_​ID=​812&​webdata_​id=​2919> [Accessed 1 Apr 2012].

go back to reference Chiang CJ, You SL, Chen CJ, Yang YW, Lo WC, Lai MS. Quality assessment and improvement of nationwide cancer registration system in Taiwan: a review. Jpn J Clin Oncol. 2015;45(3):291–6.CrossRefPubMed Chiang CJ, You SL, Chen CJ, Yang YW, Lo WC, Lai MS. Quality assessment and improvement of nationwide cancer registration system in Taiwan: a review. Jpn J Clin Oncol. 2015;45(3):291–6.CrossRefPubMed

go back to reference Lai MS. National health insurance and the way leading to better diabetes care in Taiwan. Is there a role of comprehensive analyses of the claims data? J Formos Med Assoc. 2012;111(11):587–8.CrossRefPubMed Lai MS. National health insurance and the way leading to better diabetes care in Taiwan. Is there a role of comprehensive analyses of the claims data? J Formos Med Assoc. 2012;111(11):587–8.CrossRefPubMed

go back to reference Stephanie Yasmin Brule DJJ, Christos Stelios Karapetis, Christopher J. O'Callaghan, Malcolm J. Moore, Ralph Wong, Niall C. Tebbutt, Craig, Underhill DY, John Raymond Zalcberg, Dongsheng Tu, Rachel Anne Goodwin; The Ottawa Hospital, Ottawa, ON, Canada; The Ottawa Hospital, Cancer Center O, ON, Canada; Flinders Medical Centre and Flinders Centre for Innovation in Cancer, Flinders University, Adelaide, Australia; NCIC, Clinical Trials Group K, ON, Canada; Princess Margaret Cancer Center, University Health Network, Division of Medical Oncology & Hematology,, Department of Medicine UoT, Toronto, ON, Canada; CancerCare Manitoba, Winnipeg, MB, Canada; Austin Health and University of, Melbourne H, Australia; Border Medical Oncology, Albury, Australia; Canberra and Calvary Hospitals, Canberra, Australia; Peter McCallum Hospital,, et al. Location of colon cancer (right-sided [RC] versus left-sided [LC]) as a predictor of benefit from cetuximab (CET): NCIC CTG CO.17. J Clin Oncol 31, 2013 (suppl; abstr 3528). 2013 Stephanie Yasmin Brule DJJ, Christos Stelios Karapetis, Christopher J. O'Callaghan, Malcolm J. Moore, Ralph Wong, Niall C. Tebbutt, Craig, Underhill DY, John Raymond Zalcberg, Dongsheng Tu, Rachel Anne Goodwin; The Ottawa Hospital, Ottawa, ON, Canada; The Ottawa Hospital, Cancer Center O, ON, Canada; Flinders Medical Centre and Flinders Centre for Innovation in Cancer, Flinders University, Adelaide, Australia; NCIC, Clinical Trials Group K, ON, Canada; Princess Margaret Cancer Center, University Health Network, Division of Medical Oncology & Hematology,, Department of Medicine UoT, Toronto, ON, Canada; CancerCare Manitoba, Winnipeg, MB, Canada; Austin Health and University of, Melbourne H, Australia; Border Medical Oncology, Albury, Australia; Canberra and Calvary Hospitals, Canberra, Australia; Peter McCallum Hospital,, et al. Location of colon cancer (right-sided [RC] versus left-sided [LC]) as a predictor of benefit from cetuximab (CET): NCIC CTG CO.17. J Clin Oncol 31, 2013 (suppl; abstr 3528). 2013

go back to reference Maus MK, Hanna DL, Stephens CL, Astrow SH, Yang D, Grimminger PP, et al. Distinct gene expression profiles of proximal and distal colorectal cancer: implications for cytotoxic and targeted therapy. Pharm J. 201415(4):354-62. Maus MK, Hanna DL, Stephens CL, Astrow SH, Yang D, Grimminger PP, et al. Distinct gene expression profiles of proximal and distal colorectal cancer: implications for cytotoxic and targeted therapy. Pharm J. 201415(4):354-62.

go back to reference Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med. 2004;350(23):2335–42.CrossRefPubMed Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med. 2004;350(23):2335–42.CrossRefPubMed

go back to reference Misale S, Arena S, Lamba S, Siravegna G, Lallo A, Hobor S, et al. Blockade of EGFR and MEK intercepts heterogeneous mechanisms of acquired resistance to anti-EGFR therapies in colorectal cancer. Sci Transl Med. 2014;6(224):224ra26.CrossRefPubMed Misale S, Arena S, Lamba S, Siravegna G, Lallo A, Hobor S, et al. Blockade of EGFR and MEK intercepts heterogeneous mechanisms of acquired resistance to anti-EGFR therapies in colorectal cancer. Sci Transl Med. 2014;6(224):224ra26.CrossRefPubMed

go back to reference Boisen MK, Johansen JS, Dehlendorff C, Larsen JS, Osterlind K, Hansen J, et al. Primary tumor location and bevacizumab effectiveness in patients with metastatic colorectal cancer. Ann Oncol. 2013;24(10):2554–9.CrossRefPubMed Boisen MK, Johansen JS, Dehlendorff C, Larsen JS, Osterlind K, Hansen J, et al. Primary tumor location and bevacizumab effectiveness in patients with metastatic colorectal cancer. Ann Oncol. 2013;24(10):2554–9.CrossRefPubMed

go back to reference Yamauchi M, Morikawa T, Kuchiba A, Imamura Y, Qian ZR, Nishihara R, et al. Assessment of colorectal cancer molecular features along bowel subsites challenges the conception of distinct dichotomy of proximal versus distal colorectum. Gut. 2012;61(6):847–54.CrossRefPubMedPubMedCentral Yamauchi M, Morikawa T, Kuchiba A, Imamura Y, Qian ZR, Nishihara R, et al. Assessment of colorectal cancer molecular features along bowel subsites challenges the conception of distinct dichotomy of proximal versus distal colorectum. Gut. 2012;61(6):847–54.CrossRefPubMedPubMedCentral