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Published in: Journal of Cancer Research and Clinical Oncology 5/2013

01-05-2013 | Original Paper

PIK3CA mutation is associated with poor survival among patients with metastatic colorectal cancer following anti-EGFR monoclonal antibody therapy: a meta-analysis

Authors: Shuangjie Wu, Yu Gan, Xinhai Wang, Jun Liu, Mengjun Li, Yifan Tang

Published in: Journal of Cancer Research and Clinical Oncology | Issue 5/2013

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Abstract

Purpose

PIK3CA mutation appears to predict a lack of response to anti-EGFR monoclonal antibody (mAb) treatment in patients with metastatic colorectal cancer (mCRC). However, the predictive value of PIK3CA mutations for survival remains inconclusive. Here, we pooled the data from published studies to estimate the association between PIK3CA mutation and survival outcomes in mCRC patients treated with anti-EGFR mAbs.

Methods

Studies investigating the association of PIK3CA mutations with clinical survival outcomes of mCRC patients treated with anti-EGFR mAbs were systematically identified. The overall hazard ratio (HR) was estimated by using fixed effect model or random effect model according to heterogeneity between trails.

Results

Eight studies that reported survival outcome in 839 mCRC patients were included. In unselected patients, we found that PIK3CA mutations were significantly associated with poorer PFS [8 studies, 839 patients; HR = 1.53; 95 % confidence interval (CI) 1.28–1.84; P < 0.001] and OS (5 studies; 587 patients; HR = 1.28; 95 % CI 1.05–1.56; P = 0.015). With increased predictive power in KRAS wild-type patients (3 studies; 275 patients), the overall HR for PFS was 2.44 (95 % CI 1.33–4.48; P = 0.004) and was statistically significant. We also observed a worse OS in KRAS wild-type patients with PIK3CA mutations (2 studies; 163 patients; HR = 1.37; 95 % CI 0.80–2.35; P = 0.258), although the result was not statistically significant due to small sample size.

Conclusions

PIK3CA mutation is a promising predictive biomarker for poor survival in mCRC patients treated with anti-EGFR mAbs, particularly in KRAS wild-type patients.
Literature
go back to reference Allegra C, Blanke C, Buyse M, Goldberg R, Grothey A, Meropol NJ, Saltz L, Venook A, Yothers G, Sargent D (2007) End points in advanced colon cancer clinical trials: a review and proposal. J Clin Oncol 25(24):3572–3575PubMedCrossRef Allegra C, Blanke C, Buyse M, Goldberg R, Grothey A, Meropol NJ, Saltz L, Venook A, Yothers G, Sargent D (2007) End points in advanced colon cancer clinical trials: a review and proposal. J Clin Oncol 25(24):3572–3575PubMedCrossRef
go back to reference Amado RG, Wolf M, Peeters M, Van Cutsem E, Siena S, Freeman DJ, Juan T, Sikorski R, Suggs S, Radinsky R, Patterson SD, Chang DD (2008) Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. J Clin Oncol 26(10):1626–1634PubMedCrossRef Amado RG, Wolf M, Peeters M, Van Cutsem E, Siena S, Freeman DJ, Juan T, Sikorski R, Suggs S, Radinsky R, Patterson SD, Chang DD (2008) Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. J Clin Oncol 26(10):1626–1634PubMedCrossRef
go back to reference Begg CB, Mazumdar M (1994) Operating characteristics of a rank correlation test for publication bias. Biometrics 50(4):1088–1101PubMedCrossRef Begg CB, Mazumdar M (1994) Operating characteristics of a rank correlation test for publication bias. Biometrics 50(4):1088–1101PubMedCrossRef
go back to reference Colucci G, Giuliani F, Garufi C, Mattioli R, Manzione L, Russo A, Lopez M, Parrella P, Tommasi S, Copetti M, Daniele B, Pisconti S, Tuveri G, Silvestris N, Maiello E (2010) Cetuximab plus FOLFOX-4 in untreated patients with advanced colorectal cancer: a Gruppo Oncologico dell’Italia Meridionale Multicenter phase II study. Oncology 79(5–6):415–422PubMedCrossRef Colucci G, Giuliani F, Garufi C, Mattioli R, Manzione L, Russo A, Lopez M, Parrella P, Tommasi S, Copetti M, Daniele B, Pisconti S, Tuveri G, Silvestris N, Maiello E (2010) Cetuximab plus FOLFOX-4 in untreated patients with advanced colorectal cancer: a Gruppo Oncologico dell’Italia Meridionale Multicenter phase II study. Oncology 79(5–6):415–422PubMedCrossRef
go back to reference Cunningham D, Humblet Y, Siena S, Khayat D, Bleiberg H, Santoro A, Bets D, Mueser M, Harstrick A, Verslype C, Chau I, Van Cutsem E (2004) Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med 351(4):337–345PubMedCrossRef Cunningham D, Humblet Y, Siena S, Khayat D, Bleiberg H, Santoro A, Bets D, Mueser M, Harstrick A, Verslype C, Chau I, Van Cutsem E (2004) Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med 351(4):337–345PubMedCrossRef
go back to reference De Roock W, Piessevaux H, De Schutter J, Janssens M, De Hertogh G, Personeni N, Biesmans B, Van Laethem JL, Peeters M, Humblet Y, Van Cutsem E, Tejpar S (2008) KRAS wild-type state predicts survival and is associated to early radiological response in metastatic colorectal cancer treated with cetuximab. Ann Oncol 19(3):508–515PubMedCrossRef De Roock W, Piessevaux H, De Schutter J, Janssens M, De Hertogh G, Personeni N, Biesmans B, Van Laethem JL, Peeters M, Humblet Y, Van Cutsem E, Tejpar S (2008) KRAS wild-type state predicts survival and is associated to early radiological response in metastatic colorectal cancer treated with cetuximab. Ann Oncol 19(3):508–515PubMedCrossRef
go back to reference De Roock W, Claes B, Bernasconi D, De Schutter J, Biesmans B, Fountzilas G, Kalogeras KT, Kotoula V, Papamichael D, Laurent-Puig P, Penault-Llorca F, Rougier P, Vincenzi B, Santini D, Tonini G, Cappuzzo F, Frattini M, Molinari F, Saletti P, De Dosso S, Martini M, Bardelli A, Siena S, Sartore-Bianchi A, Tabernero J, Macarulla T, Di Fiore F, Gangloff AO, Ciardiello F, Pfeiffer P, Qvortrup C, Hansen TP, Van Cutsem E, Piessevaux H, Lambrechts D, Delorenzi M, Tejpar S (2010) 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 11(8):753–762PubMedCrossRef De Roock W, Claes B, Bernasconi D, De Schutter J, Biesmans B, Fountzilas G, Kalogeras KT, Kotoula V, Papamichael D, Laurent-Puig P, Penault-Llorca F, Rougier P, Vincenzi B, Santini D, Tonini G, Cappuzzo F, Frattini M, Molinari F, Saletti P, De Dosso S, Martini M, Bardelli A, Siena S, Sartore-Bianchi A, Tabernero J, Macarulla T, Di Fiore F, Gangloff AO, Ciardiello F, Pfeiffer P, Qvortrup C, Hansen TP, Van Cutsem E, Piessevaux H, Lambrechts D, Delorenzi M, Tejpar S (2010) 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 11(8):753–762PubMedCrossRef
go back to reference Di Fiore F, Blanchard F, Charbonnier F, Le Pessot F, Lamy A, Galais MP, Bastit L, Killian A, Sesboue R, Tuech JJ, Queuniet AM, Paillot B, Sabourin JC, Michot F, Michel P, Frebourg T (2007) Clinical relevance of KRAS mutation detection in metastatic colorectal cancer treated by Cetuximab plus chemotherapy. Br J Cancer 96(8):1166–1169PubMedCrossRef Di Fiore F, Blanchard F, Charbonnier F, Le Pessot F, Lamy A, Galais MP, Bastit L, Killian A, Sesboue R, Tuech JJ, Queuniet AM, Paillot B, Sabourin JC, Michot F, Michel P, Frebourg T (2007) Clinical relevance of KRAS mutation detection in metastatic colorectal cancer treated by Cetuximab plus chemotherapy. Br J Cancer 96(8):1166–1169PubMedCrossRef
go back to reference Di Fiore F, Sesboue R, Michel P, Sabourin JC, Frebourg T (2010) Molecular determinants of anti-EGFR sensitivity and resistance in metastatic colorectal cancer. Br J Cancer 103(12):1765–1772PubMedCrossRef Di Fiore F, Sesboue R, Michel P, Sabourin JC, Frebourg T (2010) Molecular determinants of anti-EGFR sensitivity and resistance in metastatic colorectal cancer. Br J Cancer 103(12):1765–1772PubMedCrossRef
go back to reference Garrido-Laguna I, Hong DS, Janku F, Nguyen LM, Falchook GS, Fu S, Wheler JJ, Luthra R, Naing A, Wang X, Kurzrock R (2012) KRASness and PIK3CAness in patients with advanced colorectal cancer: outcome after treatment with early-phase trials with targeted pathway inhibitors. PLoS ONE 7(5):e38033PubMedCrossRef Garrido-Laguna I, Hong DS, Janku F, Nguyen LM, Falchook GS, Fu S, Wheler JJ, Luthra R, Naing A, Wang X, Kurzrock R (2012) KRASness and PIK3CAness in patients with advanced colorectal cancer: outcome after treatment with early-phase trials with targeted pathway inhibitors. PLoS ONE 7(5):e38033PubMedCrossRef
go back to reference Goldberg RM, Rothenberg ML, Van Cutsem E, Benson AB 3rd, Blanke CD, Diasio RB, Grothey A, Lenz HJ, Meropol NJ, Ramanathan RK, Becerra CH, Wickham R, Armstrong D, Viele C (2007) The continuum of care: a paradigm for the management of metastatic colorectal cancer. Oncologist 12(1):38–50PubMedCrossRef Goldberg RM, Rothenberg ML, Van Cutsem E, Benson AB 3rd, Blanke CD, Diasio RB, Grothey A, Lenz HJ, Meropol NJ, Ramanathan RK, Becerra CH, Wickham R, Armstrong D, Viele C (2007) The continuum of care: a paradigm for the management of metastatic colorectal cancer. Oncologist 12(1):38–50PubMedCrossRef
go back to reference Grothey A, Sugrue MM, Purdie DM, Dong W, Sargent D, Hedrick E, Kozloff M (2008) Bevacizumab beyond first progression is associated with prolonged overall survival in metastatic colorectal cancer: results from a large observational cohort study (BRiTE). J Clin Oncol 26(33):5326–5334PubMedCrossRef Grothey A, Sugrue MM, Purdie DM, Dong W, Sargent D, Hedrick E, Kozloff M (2008) Bevacizumab beyond first progression is associated with prolonged overall survival in metastatic colorectal cancer: results from a large observational cohort study (BRiTE). J Clin Oncol 26(33):5326–5334PubMedCrossRef
go back to reference Hayashi H, Okamoto I, Morita S, Taguri M, Nakagawa K (2012) Post progression survival for first-line chemotherapy of patients with advanced non-small-cell lung cancer. Ann Oncol 23(6):1537–1541PubMedCrossRef Hayashi H, Okamoto I, Morita S, Taguri M, Nakagawa K (2012) Post progression survival for first-line chemotherapy of patients with advanced non-small-cell lung cancer. Ann Oncol 23(6):1537–1541PubMedCrossRef
go back to reference He Y, Van’t Veer LJ, Mikolajewska-Hanclich I, van Velthuysen ML, Zeestraten EC, Nagtegaal ID, van de Velde CJ, Marijnen CA (2009) PIK3CA mutations predict local recurrences in rectal cancer patients. Clin Cancer Res 15(22):6956–6962PubMedCrossRef He Y, Van’t Veer LJ, Mikolajewska-Hanclich I, van Velthuysen ML, Zeestraten EC, Nagtegaal ID, van de Velde CJ, Marijnen CA (2009) PIK3CA mutations predict local recurrences in rectal cancer patients. Clin Cancer Res 15(22):6956–6962PubMedCrossRef
go back to reference Ikenoue T, Kanai F, Hikiba Y, Obata T, Tanaka Y, Imamura J, Ohta M, Jazag A, Guleng B, Tateishi K, Asaoka Y, Matsumura M, Kawabe T, Omata M (2005) Functional analysis of PIK3CA gene mutations in human colorectal cancer. Cancer Res 65(11):4562–4567PubMedCrossRef Ikenoue T, Kanai F, Hikiba Y, Obata T, Tanaka Y, Imamura J, Ohta M, Jazag A, Guleng B, Tateishi K, Asaoka Y, Matsumura M, Kawabe T, Omata M (2005) Functional analysis of PIK3CA gene mutations in human colorectal cancer. Cancer Res 65(11):4562–4567PubMedCrossRef
go back to reference Kang S, Bader AG, Vogt PK (2005) Phosphatidylinositol 3-kinase mutations identified in human cancer are oncogenic. Proc Natl Acad Sci U S A 102(3):802–807PubMedCrossRef Kang S, Bader AG, Vogt PK (2005) Phosphatidylinositol 3-kinase mutations identified in human cancer are oncogenic. Proc Natl Acad Sci U S A 102(3):802–807PubMedCrossRef
go back to reference Lievre A, Bachet JB, Boige V, Cayre A, Le Corre D, Buc E, Ychou M, Bouche O, Landi B, Louvet C, Andre T, Bibeau F, Diebold MD, Rougier P, Ducreux M, Tomasic G, Emile JF, Penault-Llorca F, Laurent-Puig P (2008) KRAS mutations as an independent prognostic factor in patients with advanced colorectal cancer treated with cetuximab. J Clin Oncol 26(3):374–379PubMedCrossRef Lievre A, Bachet JB, Boige V, Cayre A, Le Corre D, Buc E, Ychou M, Bouche O, Landi B, Louvet C, Andre T, Bibeau F, Diebold MD, Rougier P, Ducreux M, Tomasic G, Emile JF, Penault-Llorca F, Laurent-Puig P (2008) KRAS mutations as an independent prognostic factor in patients with advanced colorectal cancer treated with cetuximab. J Clin Oncol 26(3):374–379PubMedCrossRef
go back to reference Mao C, Yang ZY, Hu XF, Chen Q, Tang JL (2012) PIK3CA exon 20 mutations as a potential biomarker for resistance to anti-EGFR monoclonal antibodies in KRAS wild-type metastatic colorectal cancer: a systematic review and meta-analysis. Ann Oncol 23(6):1518–1525PubMedCrossRef Mao C, Yang ZY, Hu XF, Chen Q, Tang JL (2012) PIK3CA exon 20 mutations as a potential biomarker for resistance to anti-EGFR monoclonal antibodies in KRAS wild-type metastatic colorectal cancer: a systematic review and meta-analysis. Ann Oncol 23(6):1518–1525PubMedCrossRef
go back to reference Meyerhardt JA, Mayer RJ (2005) Systemic therapy for colorectal cancer. N Engl J Med 352(5):476–487PubMedCrossRef Meyerhardt JA, Mayer RJ (2005) Systemic therapy for colorectal cancer. N Engl J Med 352(5):476–487PubMedCrossRef
go back to reference Moroni M, Veronese S, Benvenuti S, Marrapese G, Sartore-Bianchi A, Di Nicolantonio F, Gambacorta M, Siena S, Bardelli A (2005) Gene copy number for epidermal growth factor receptor (EGFR) and clinical response to antiEGFR treatment in colorectal cancer: a cohort study. Lancet Oncol 6(5):279–286PubMedCrossRef Moroni M, Veronese S, Benvenuti S, Marrapese G, Sartore-Bianchi A, Di Nicolantonio F, Gambacorta M, Siena S, Bardelli A (2005) Gene copy number for epidermal growth factor receptor (EGFR) and clinical response to antiEGFR treatment in colorectal cancer: a cohort study. Lancet Oncol 6(5):279–286PubMedCrossRef
go back to reference Nosho K, Kawasaki T, Ohnishi M, Suemoto Y, Kirkner GJ, Zepf D, Yan L, Longtine JA, Fuchs CS, Ogino S (2008) PIK3CA mutation in colorectal cancer: relationship with genetic and epigenetic alterations. Neoplasia 10(6):534–541PubMed Nosho K, Kawasaki T, Ohnishi M, Suemoto Y, Kirkner GJ, Zepf D, Yan L, Longtine JA, Fuchs CS, Ogino S (2008) PIK3CA mutation in colorectal cancer: relationship with genetic and epigenetic alterations. Neoplasia 10(6):534–541PubMed
go back to reference Parmar MK, Torri V, Stewart L (1998) Extracting summary statistics to perform meta-analyses of the published literature for survival endpoints. Stat Med 17(24):2815–2834PubMedCrossRef Parmar MK, Torri V, Stewart L (1998) Extracting summary statistics to perform meta-analyses of the published literature for survival endpoints. Stat Med 17(24):2815–2834PubMedCrossRef
go back to reference Perrone F, Lampis A, Orsenigo M, Di Bartolomeo M, Gevorgyan A, Losa M, Frattini M, Riva C, Andreola S, Bajetta E, Bertario L, Leo E, Pierotti MA, Pilotti S (2009) PI3KCA/PTEN deregulation contributes to impaired responses to cetuximab in metastatic colorectal cancer patients. Ann Oncol 20(1):84–90PubMedCrossRef Perrone F, Lampis A, Orsenigo M, Di Bartolomeo M, Gevorgyan A, Losa M, Frattini M, Riva C, Andreola S, Bajetta E, Bertario L, Leo E, Pierotti MA, Pilotti S (2009) PI3KCA/PTEN deregulation contributes to impaired responses to cetuximab in metastatic colorectal cancer patients. Ann Oncol 20(1):84–90PubMedCrossRef
go back to reference Prenen H, De Schutter J, Jacobs B, De Roock W, Biesmans B, Claes B, Lambrechts D, Van Cutsem E, Tejpar S (2009) PIK3CA mutations are not a major determinant of resistance to the epidermal growth factor receptor inhibitor cetuximab in metastatic colorectal cancer. Clin Cancer Res 15(9):3184–3188PubMedCrossRef Prenen H, De Schutter J, Jacobs B, De Roock W, Biesmans B, Claes B, Lambrechts D, Van Cutsem E, Tejpar S (2009) PIK3CA mutations are not a major determinant of resistance to the epidermal growth factor receptor inhibitor cetuximab in metastatic colorectal cancer. Clin Cancer Res 15(9):3184–3188PubMedCrossRef
go back to reference Saad ED, Katz A (2009) Progression-free survival and time to progression as primary end points in advanced breast cancer: often used, sometimes loosely defined. Ann Oncol 20(3):460–464PubMedCrossRef Saad ED, Katz A (2009) Progression-free survival and time to progression as primary end points in advanced breast cancer: often used, sometimes loosely defined. Ann Oncol 20(3):460–464PubMedCrossRef
go back to reference Sargent DJ, Wieand HS, Haller DG, Gray R, Benedetti JK, Buyse M, Labianca R, Seitz JF, O’Callaghan CJ, Francini G, Grothey A, O’Connell M, Catalano PJ, Blanke CD, Kerr D, Green E, Wolmark N, Andre T, Goldberg RM, De Gramont A (2005) Disease-free survival versus overall survival as a primary end point for adjuvant colon cancer studies: individual patient data from 20,898 patients on 18 randomized trials. J Clin Oncol 23(34):8664–8670PubMedCrossRef Sargent DJ, Wieand HS, Haller DG, Gray R, Benedetti JK, Buyse M, Labianca R, Seitz JF, O’Callaghan CJ, Francini G, Grothey A, O’Connell M, Catalano PJ, Blanke CD, Kerr D, Green E, Wolmark N, Andre T, Goldberg RM, De Gramont A (2005) Disease-free survival versus overall survival as a primary end point for adjuvant colon cancer studies: individual patient data from 20,898 patients on 18 randomized trials. J Clin Oncol 23(34):8664–8670PubMedCrossRef
go back to reference Saridaki Z, Tzardi M, Papadaki C, Sfakianaki M, Pega F, Kalikaki A, Tsakalaki E, Trypaki M, Messaritakis I, Stathopoulos E, Mavroudis D, Georgoulias V, Souglakos J (2011) Impact of KRAS, BRAF, PIK3CA mutations, PTEN, AREG, EREG expression and skin rash in >/=2 line cetuximab-based therapy of colorectal cancer patients. PLoS ONE 6(1):e15980PubMedCrossRef Saridaki Z, Tzardi M, Papadaki C, Sfakianaki M, Pega F, Kalikaki A, Tsakalaki E, Trypaki M, Messaritakis I, Stathopoulos E, Mavroudis D, Georgoulias V, Souglakos J (2011) Impact of KRAS, BRAF, PIK3CA mutations, PTEN, AREG, EREG expression and skin rash in >/=2 line cetuximab-based therapy of colorectal cancer patients. PLoS ONE 6(1):e15980PubMedCrossRef
go back to reference Sartore-Bianchi A, Di Nicolantonio F, Nichelatti M, Molinari F, De Dosso S, Saletti P, Martini M, Cipani T, Marrapese G, Mazzucchelli L, Lamba S, Veronese S, Frattini M, Bardelli A, Siena S (2009) Multi-determinants analysis of molecular alterations for predicting clinical benefit to EGFR-targeted monoclonal antibodies in colorectal cancer. PLoS ONE 4(10):e7287PubMedCrossRef Sartore-Bianchi A, Di Nicolantonio F, Nichelatti M, Molinari F, De Dosso S, Saletti P, Martini M, Cipani T, Marrapese G, Mazzucchelli L, Lamba S, Veronese S, Frattini M, Bardelli A, Siena S (2009) Multi-determinants analysis of molecular alterations for predicting clinical benefit to EGFR-targeted monoclonal antibodies in colorectal cancer. PLoS ONE 4(10):e7287PubMedCrossRef
go back to reference Sood A, McClain D, Maitra R, Basu-Mallick A, Seetharam R, Kaubisch A, Rajdev L, Mariadason JM, Tanaka K, Goel S (2012) PTEN gene expression and mutations in the PIK3CA gene as predictors of clinical benefit to anti-epidermal growth factor receptor antibody therapy in patients with KRAS wild-type metastatic colorectal cancer. Clin Colorectal Cancer 11(2):143–150PubMedCrossRef Sood A, McClain D, Maitra R, Basu-Mallick A, Seetharam R, Kaubisch A, Rajdev L, Mariadason JM, Tanaka K, Goel S (2012) PTEN gene expression and mutations in the PIK3CA gene as predictors of clinical benefit to anti-epidermal growth factor receptor antibody therapy in patients with KRAS wild-type metastatic colorectal cancer. Clin Colorectal Cancer 11(2):143–150PubMedCrossRef
go back to reference Souglakos J, Philips J, Wang R, Marwah S, Silver M, Tzardi M, Silver J, Ogino S, Hooshmand S, Kwak E, Freed E, Meyerhardt JA, Saridaki Z, Georgoulias V, Finkelstein D, Fuchs CS, Kulke MH, Shivdasani RA (2009) Prognostic and predictive value of common mutations for treatment response and survival in patients with metastatic colorectal cancer. Br J Cancer 101(3):465–472PubMedCrossRef Souglakos J, Philips J, Wang R, Marwah S, Silver M, Tzardi M, Silver J, Ogino S, Hooshmand S, Kwak E, Freed E, Meyerhardt JA, Saridaki Z, Georgoulias V, Finkelstein D, Fuchs CS, Kulke MH, Shivdasani RA (2009) Prognostic and predictive value of common mutations for treatment response and survival in patients with metastatic colorectal cancer. Br J Cancer 101(3):465–472PubMedCrossRef
go back to reference Tol J, Dijkstra JR, Klomp M, Teerenstra S, Dommerholt M, Vink-Borger ME, van Cleef PH, van Krieken JH, Punt CJ, Nagtegaal ID (2010) Markers for EGFR pathway activation as predictor of outcome in metastatic colorectal cancer patients treated with or without cetuximab. Eur J Cancer 46(11):1997–2009PubMedCrossRef Tol J, Dijkstra JR, Klomp M, Teerenstra S, Dommerholt M, Vink-Borger ME, van Cleef PH, van Krieken JH, Punt CJ, Nagtegaal ID (2010) Markers for EGFR pathway activation as predictor of outcome in metastatic colorectal cancer patients treated with or without cetuximab. Eur J Cancer 46(11):1997–2009PubMedCrossRef
go back to reference Ulivi P, Capelli L, Valgiusti M, Zoli W, Scarpi E, Chiadini E, Rosetti P, Bravaccini S, Calistri D, Saragoni L, Gardini AC, Ragazzini A, Frassineti GL, Amadori D, Passardi A (2012) Predictive role of multiple gene alterations in response to cetuximab in metastatic colorectal cancer: a single center study. J Transl Med 10:87PubMedCrossRef Ulivi P, Capelli L, Valgiusti M, Zoli W, Scarpi E, Chiadini E, Rosetti P, Bravaccini S, Calistri D, Saragoni L, Gardini AC, Ragazzini A, Frassineti GL, Amadori D, Passardi A (2012) Predictive role of multiple gene alterations in response to cetuximab in metastatic colorectal cancer: a single center study. J Transl Med 10:87PubMedCrossRef
go back to reference Van Cutsem E, Peeters M, Siena S, Humblet Y, Hendlisz A, Neyns B, Canon JL, Van Laethem JL, Maurel J, Richardson G, Wolf M, Amado RG (2007) Open-label phase III trial of panitumumab plus best supportive care compared with best supportive care alone in patients with chemotherapy-refractory metastatic colorectal cancer. J Clin Oncol 25(13):1658–1664PubMedCrossRef Van Cutsem E, Peeters M, Siena S, Humblet Y, Hendlisz A, Neyns B, Canon JL, Van Laethem JL, Maurel J, Richardson G, Wolf M, Amado RG (2007) Open-label phase III trial of panitumumab plus best supportive care compared with best supportive care alone in patients with chemotherapy-refractory metastatic colorectal cancer. J Clin Oncol 25(13):1658–1664PubMedCrossRef
go back to reference Van Cutsem E, Kohne CH, Hitre E, Zaluski J, Chang Chien CR, Makhson A, D’Haens G, Pinter T, Lim R, Bodoky G, Roh JK, Folprecht G, Ruff P, Stroh C, Tejpar S, Schlichting M, Nippgen J, Rougier P (2009) Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med 360(14):1408–1417PubMedCrossRef Van Cutsem E, Kohne CH, Hitre E, Zaluski J, Chang Chien CR, Makhson A, D’Haens G, Pinter T, Lim R, Bodoky G, Roh JK, Folprecht G, Ruff P, Stroh C, Tejpar S, Schlichting M, Nippgen J, Rougier P (2009) Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med 360(14):1408–1417PubMedCrossRef
Metadata
Title
PIK3CA mutation is associated with poor survival among patients with metastatic colorectal cancer following anti-EGFR monoclonal antibody therapy: a meta-analysis
Authors
Shuangjie Wu
Yu Gan
Xinhai Wang
Jun Liu
Mengjun Li
Yifan Tang
Publication date
01-05-2013
Publisher
Springer-Verlag
Published in
Journal of Cancer Research and Clinical Oncology / Issue 5/2013
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI
https://doi.org/10.1007/s00432-013-1400-x

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