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Targeted Oncology

Erschienen in:

01.06.2013 | Review

Role of targeted agents in metastatic colorectal cancer

verfasst von: Hans Prenen, Loredana Vecchione, Eric Van Cutsem

Erschienen in: Targeted Oncology | Ausgabe 2/2013

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Abstract

Despite a decrease in incidence and mortality, colorectal cancer (CRC) still represents the second leading cause of cancer worldwide. Recurrence following surgery and adjuvant treatment and the metastatic disease are still a major problem with a median overall survival of approximately 24 months. Nevertheless, there has been an improvement in outcome due to the introduction into clinical practice of new cytotoxic and targeted agents. The targeted agents that have improved the efficacy of the available chemotherapeutic regimens in CRC are the ones that target the vascular endothelial growth factor (VEGF) and the epidermal growth factor receptor (EGFR). In particular, bevacizumab, a recombinant humanized monoclonal antibody against VEGF, cetuximab, and panitumumab, two monoclonal antibodies that target the EGFR, have been approved for the treatment of metastatic CRC (mCRC). While for anti-EGFR agents, predictive biomarkers have been found, no good biomarkers have been found yet for anti-VEGF agents. Aflibercept and regorafenib have recently also been approved in patients with mCRC. This article reviews in an extensive way the data of large randomized clinical trials for the use of anti-VEGF and anti-EGFR in CRC. Aim of this review is also to describe the current status of biomarkers discovery and highlight how to improve the therapeutic index of these targeted agents by selecting in advance the subgroup of patients who will benefit from these treatments.

Siegel R, Ward E, Brawley O, Jemal A (2011) Cancer statistics, 2011: the impact of eliminating socioeconomic and racial disparities on premature cancer deaths. CA Cancer J Clin 61:212–236PubMedCrossRef

Cheng L, Eng C, Nieman LZ, Kapadia AS, Du XL (2011) Trends in colorectal cancer incidence by anatomic site and disease stage in the US from 1976 to 2005. Am J Clin Oncol 34:573–580PubMedCrossRef

Poston GJ, Figueras J, Giuliante F, Nuzzo G, Sobrero AF, Gigot JF, Nordlinger B, Adam R, Gruenberger T, Choti MA, Bilchik AJ, Van Cutsem EJ, Chiang JM, D’Angelica MI (2008) Urgent need for a new staging system in advanced colorectal cancer. J Clin Oncol 26:4828–4833PubMedCrossRef

Tournigand C, Andre T, Achille E, Lledo G, Flesh M, Mery-Mignard D, Quinaux E, Couteau C, Buyse M, Ganem G, Landi B, Colin P, Louvet C, de Gramont A (2004) FOLFIRI followed by FOLFOX6 or the reverse sequence in advanced colorectal cancer: a randomized GERCOR study. J Clin Oncol 22:229–237PubMedCrossRef

Colucci G, Gebbia V, Paoletti G, Giuliani F, Caruso M, Gebbia N, Carteni G, Agostara B, Pezzella G, Manzione L, Borsellino N, Misino A, Romito S, Durini E, Cordio S, Di SM, Lopez M, Maiello E, Montemurro S, Cramarossa A, Lorusso V, Di BM, Chiarenza M, Valerio MR, Guida T, Leonardi V, Pisconti S, Rosati G, Carrozza F, Nettis G, Valdesi M, Filippelli G, Fortunato S, Mancarella S, Brunetti C (2005) Phase III randomized trial of FOLFIRI versus FOLFOX4 in the treatment of advanced colorectal cancer: a multicenter study of the Gruppo Oncologico Dell’Italia Meridionale. J Clin Oncol 23:4866–4875PubMedCrossRef

Van Cutsem E, Rivera F, Berry S, Kretzschmar A, Michael M, DiBartolomeo M, Mazier MA, Canon JL, Georgoulias V, Peeters M, Bridgewater J, Cunningham D (2009) Safety and efficacy of first-line bevacizumab with FOLFOX, XELOX, FOLFIRI, and fluoropyrimidines in metastatic colorectal cancer: the BEAT study. Ann Oncol 20:1842–1847PubMedCrossRef

Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W, Berlin J, Baron A, Griffing S, Holmgren E, Ferrara N, Fyfe G, Rogers B, Ross R, Kabbinavar F (2004) Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 350:2335–2342PubMedCrossRef

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 360:1408–1417PubMedCrossRef

Van Cutsem E, Kohne CH, Lang I, Folprecht G, Nowacki MP, Cascinu S, Shchepotin I, Maurel J, Cunningham D, Tejpar S, Schlichting M, Zubel A, Celik I, Rougier P, Ciardiello F (2011) 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 29:2011–2019PubMedCrossRef

10.

Amado RG, Wolf M, Peeters M, Van CE, 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 26:1626–1634PubMedCrossRef

11.

Welch S, Spithoff K, Rumble RB, Maroun J (2010) Bevacizumab combined with chemotherapy for patients with advanced colorectal cancer: a systematic review. Ann Oncol 21:1152–1162PubMedCrossRef

12.

Bennouna J, Sastre J, Arnold D, Osterlund P, Greil R, Van Cutsem E, von Moos R, Vieitez JM, Bouche O, Borg C, Steffens CC, Alonso-Orduna V, Schlichting C, Reyes-Rivera I, Bendahmane B, Andre T, Kubicka S (2013) Continuation of bevacizumab after first progression in metastatic colorectal cancer (ML18147): a randomized phase 3 trial. Lancet Oncol 14:29–37PubMedCrossRef

13.

Bokemeyer C, Bondarenko I, Makhson A, Hartmann JT, Aparicio J, de Braud F, Donea S, Ludwig H, Schuch G, Stroh C, Loos AH, Zubel A, Koralewski P (2009) Fluorouracil, leucovorin, and oxaliplatin with and without cetuximab in the first-line treatment of metastatic colorectal cancer. J Clin Oncol 27:663–671PubMedCrossRef

14.

Douillard JY, Siena S, Cassidy J, Tabernero J, Burkes R, Barugel M, Humblet Y, Bodoky G, Cunningham D, Jassem J, Rivera F, Kocakova I, Ruff P, Blasinska-Morawiec M, Smakal M, Canon JL, Rother M, Oliner KS, Wolf M, Gansert J (2010) Randomized phase III trial of panitumumab with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer: the PRIME study. J Clin Oncol 28:4697–4705PubMedCrossRef

15.

Jonker DJ, O’Callaghan CJ, Karapetis CS, Zalcberg JR, Tu D, Au HJ, Berry SR, Krahn M, Price T, Simes RJ, Tebbutt NC, Van HG, Wierzbicki R, Langer C, Moore MJ (2007) Cetuximab for the treatment of colorectal cancer. N Engl J Med 357:2040–2048PubMedCrossRef

16.

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 351:337–345PubMedCrossRef

17.

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 11:753–762PubMedCrossRef

18.

Grothey A, Van Cutsem E, Sobrero A, Siena S, Falcone A, Ychou M, Humblet Y, Bouche O, Mineur L, Barone C, Adenis A, Tabernero J, Yoshino T, Lenz HJ, Goldberg RM, Sargent DJ, Cihon F, Cupit L, Wagner A, Laurent D (2013) Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomized, placebo-controlled, phase 3 trial. Lancet 381:303–312PubMedCrossRef

19.

Van Cutsem E, Tabernero J, Lakomy R, Prenen H, Prausova J, Macarulla T, Ruff P, van Hazel GA, Moiseyenko V, Ferry D, McKendrick J, Polikoff J, Tellier A, Castan R, Allegra C (2012) Addition of aflibercept to fluorouracil, leucovorin, and irinotecan improves survival in a phase III randomized trial in patients with metastatic colorectal cancer previously treated with an oxaliplatin-based regimen. J Clin Oncol 30:3499–3506PubMedCrossRef

20.

Carmeliet P, Moons L, Luttun A, Vincenti V, Compernolle V, De Mol M, Wu Y, Bono F, Devy L, Beck H, Scholz D, Acker T, DiPalma T, Dewerchin M, Noel A, Stalmans I, Barra A, Blacher S, VandenDriessche T, Ponten A, Eriksson U, Plate KH, Foidart JM, Schaper W, Charnock-Jones DS, Hicklin DJ, Herbert JM, Collen D, Persico MG (2001) Synergism between vascular endothelial growth factor and placental growth factor contributes to angiogenesis and plasma extravasation in pathological conditions. Nat Med 7:575–583PubMedCrossRef

21.

Bagri A, Tessier-Lavigne M, Watts RJ (2009) Neuropilins in tumor biology. Clin Cancer Res 15:1860–1864PubMedCrossRef

22.

Rizzolio S, Rabinowicz N, Rainero E, Lanzetti L, Serini G, Norman J, Neufeld G, Tamagnone L (2012) Neuropilin-1-dependent regulation of EGF-receptor signaling. Cancer Res 72:5801–5811PubMedCrossRef

23.

Ellis LM, Hicklin DJ (2008) VEGF-targeted therapy: mechanisms of anti-tumor activity. Nat Rev Cancer 8:579–591PubMedCrossRef

24.

Gordon MS, Margolin K, Talpaz M, Sledge GW Jr, Holmgren E, Benjamin R, Stalter S, Shak S, Adelman D (2001) Phase I safety and pharmacokinetic study of recombinant human antivascular endothelial growth factor in patients with advanced cancer. J Clin Oncol 19:843–850PubMed

25.

Tejpar S, Prenen H, Mazzone M (2012) Overcoming resistance to anti-angiogenic therapies. Oncologist 17:1039–1050PubMedCrossRef

26.

Fuchs CS, Marshall J, Barrueco J (2008) Randomized, controlled trial of irinotecan plus infusional, bolus, or oral fluoropyrimidines in first-line treatment of metastatic colorectal cancer: updated results from the BICC-C study. J Clin Oncol 26:689–690PubMedCrossRef

27.

Stathopoulos GP, Batziou C, Trafalis D, Koutantos J, Batzios S, Stathopoulos J, Legakis J, Armakolas A (2010) Treatment of colorectal cancer with and without bevacizumab: a phase III study. Oncology 78:376–381PubMedCrossRef

28.

Saltz LB, Clarke S, Diaz-Rubio E, Scheithauer W, Figer A, Wong R, Koski S, Lichinitser M, Yang TS, Rivera F, Couture F, Sirzen F, Cassidy J (2008) Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study. J Clin Oncol 26:2013–2019PubMedCrossRef

29.

Price TJ, Hardingham JE, Lee CK, Weickhardt A, Townsend AR, Wrin JW, Chua A, Shivasami A, Cummins MM, Murone C, Tebbutt NC (2011) Impact of KRAS and BRAF gene mutation status on outcomes from the phase III AGITG max trial of capecitabine alone or in combination with bevacizumab and mitomycin in advanced colorectal cancer. J Clin Oncol 29:2675–2682PubMedCrossRef

30.

Cunningham D, Lang I, Lorusso V, Ocvirk J, Shin D, Jonker DJ, Osborne S, Andre NA, Waterkamp D, Saunders MP (2012) Bevacizumab (bev) in combination with capecitabine (cape) for the first-line treatment of elderly patients with metastatic colorectal cancer (mCRC): Results of a randomized international phase III trial (AVEX) J Clin Oncol 30 (suppl 34: abstr 337)

31.

Giantonio BJ, Catalano PJ, Meropol NJ, O’Dwyer PJ, Mitchell EP, Alberts SR, Schwartz MA, Benson AB III (2007) Bevacizumab in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) for previously treated metastatic colorectal cancer: results from the Eastern cooperative oncology group study E3200. J Clin Oncol 25:1539–1544PubMedCrossRef

32.

Masi G, loupakis F, Salvatore L, Cremolini C, Fornaro L, Schirripa M, Fea E, Granetto C, Antonuzzo L, Giommoni E, Allegrini G, Cupini S, Boni C, Banzi M, Chiara S, Sonaglio C, Valsuani C, Bonetti A, Boni L, Falcone A (2012) A randomized phase III study evaluating the continuation of bevacizumab (BV) beyond progression in metastatic colorectal cancer (mCRC) patients (pts) who received BV as part of first-line treatment: results of the BEBYP trial by the Gruppo Oncologico Nord (ESMO 2012 LB abstract 2734)

33.

Grothey A, Sargent D, Goldberg RM, Schmoll HJ (2004) Survival of patients with advanced colorectal cancer improves with the availability of fluorouracil–leucovorin, irinotecan, and oxaliplatin in the course of treatment. J Clin Oncol 22:1209–1214PubMedCrossRef

34.

Lievre A, Samalin E, Mitry E, Assenat E, Boyer-Gestin C, Lepere C, Bachet JB, Portales F, Vaillant JN, Ychou M, Rougier P (2009) Bevacizumab plus FOLFIRI or FOLFOX in chemotherapy-refractory patients with metastatic colorectal cancer: a retrospective study. BMC Cancer 9:347PubMedCrossRef

35.

Chen HX, Mooney M, Boron M, Vena D, Mosby K, Grochow L, Jaffe C, Rubinstein L, Zwiebel J, Kaplan RS (2006) Phase II multicenter trial of bevacizumab plus fluorouracil and leucovorin in patients with advanced refractory colorectal cancer: an NCI treatment referral center trial TRC-0301. J Clin Oncol 24:3354–3360PubMedCrossRef

36.

Vincenzi B, Santini D, Russo A, Spoto C, Venditti O, Gasparro S, Rizzo S, Zobel BB, Caricato M, Valeri S, Coppola R, Tonini G (2009) Bevacizumab in association with de Gramont 5-fluorouracil/folic acid in patients with oxaliplatin-, irinotecan-, and cetuximab-refractory colorectal cancer: a single-center phase 2 trial. Cancer 115:4849–4856PubMedCrossRef

37.

Kang BW, Kim TW, Lee JL, Ryu MH, Chang HM, Yu CS, Kim JC, Kim JH, Kang YK (2009) Bevacizumab plus FOLFIRI or FOLFOX as third-line or later treatment in patients with metastatic colorectal cancer after failure of 5-fluorouracil, irinotecan, and oxaliplatin: a retrospective analysis. Med Oncol 26:32–37PubMedCrossRef

38.

Geva R, Vecchione L, Tejpar S, Piessevaux H, Van Cutsem E, Prenen H (2013) Bevacizumab plus chemotherapy as salvage treatment in chemorefractory patients with metastatic colorectal cancer. Onco Targets Ther 6:53–58PubMed

39.

Viloria-Petit A, Crombet T, Jothy S, Hicklin D, Bohlen P, Schlaeppi JM, Rak J, Kerbel RS (2001) Acquired resistance to the antitumor effect of epidermal growth factor receptor-blocking antibodies in vivo: a role for altered tumor angiogenesis. Cancer Res 61:5090–5101PubMed

40.

Chu QS (2009) Aflibercept (AVE0005): an alternative strategy for inhibiting tumor angiogenesis by vascular endothelial growth factors. Expert Opin Biol Ther 9:263–271PubMedCrossRef

41.

Strumberg D, Schultheis B (2012) Regorafenib for cancer. Expert Opin Investig Drugs 21:879–889PubMedCrossRef

42.

Jain RK, Duda DG, Willett CG, Sahani DV, Zhu AX, Loeffler JS, Batchelor TT, Sorensen AG (2009) Biomarkers of response and resistance to anti-angiogenic therapy. Nat Rev Clin Oncol 6:327–338PubMedCrossRef

43.

Kopetz S, Hoff PM, Morris JS, Wolff RA, Eng C, Glover KY, Adinin R, Overman MJ, Valero V, Wen S, Lieu C, Yan S, Tran HT, Ellis LM, Abbruzzese JL, Heymach JV (2010) Phase II trial of infusional fluorouracil, irinotecan, and bevacizumab for metastatic colorectal cancer: efficacy and circulating angiogenic biomarkers associated with therapeutic resistance. J Clin Oncol 28:453–459PubMedCrossRef

44.

Schneider BP, Shen F, Miller KD (2012) Pharmacogenetic biomarkers for the prediction of response to anti-angiogenic treatment. Lancet Oncol 13:e427–e436PubMedCrossRef

45.

Lambrechts D, Claes B, Delmar P, Reumers J, Mazzone M, Yesilyurt BT, Devlieger R, Verslype C, Tejpar S, Wildiers H, de Haas S, Carmeliet P, Scherer SJ, Van Cutsem E (2012) VEGF pathway genetic variants as biomarkers of treatment outcome with bevacizumab: an analysis of data from the AViTA and AVOREN randomized trials. Lancet Oncol 13:724–733PubMedCrossRef

46.

Wood LD, Parsons DW, Jones S, Lin J, Sjoblom T, Leary RJ, Shen D, Boca SM, Barber T, Ptak J, Silliman N, Szabo S, Dezso Z, Ustyanksky V, Nikolskaya T, Nikolsky Y, Karchin R, Wilson PA, Kaminker JS, Zhang Z, Croshaw R, Willis J, Dawson D, Shipitsin M, Willson JK, Sukumar S, Polyak K, Park BH, Pethiyagoda CL, Pant PV, Ballinger DG, Sparks AB, Hartigan J, Smith DR, Suh E, Papadopoulos N, Buckhaults P, Markowitz SD, Parmigiani G, Kinzler KW, Velculescu VE, Vogelstein B (2007) The genomic landscapes of human breast and colorectal cancers. Science 318:1108–1113PubMedCrossRef

47.

Yarden Y (2001) The EGFR family and its ligands in human cancer. signaling mechanisms and therapeutic opportunities. Eur J Cancer 37(Suppl 4):S3–S8PubMedCrossRef

48.

Yarden Y, Sliwkowski MX (2001) Untangling the ERBB signaling network. Nat Rev Mol Cell Biol 2:127–137PubMedCrossRef

49.

Ciardiello F, Tortora G (2008) EGFR antagonists in cancer treatment. N Engl J Med 358:1160–1174PubMedCrossRef

50.

Fiske WH, Threadgill D, Coffey RJ (2009) ERBBs in the gastrointestinal tract: recent progress and new perspectives. Exp Cell Res 315:583–601PubMedCrossRef

51.

Roberts RB, Min L, Washington MK, Olsen SJ, Settle SH, Coffey RJ, Threadgill DW (2002) Importance of epidermal growth factor receptor signaling in establishment of adenomas and maintenance of carcinomas during intestinal tumorigenesis. Proc Natl Acad Sci U S A 99:1521–1526PubMedCrossRef

52.

Erwin CR, Helmrath MA, Shin CE, Falcone RA Jr, Stern LE, Warner BW (1999) Intestinal overexpression of EGF in transgenic mice enhances adaptation after small bowel resection. Am J Physiol 277:G533–G540PubMed

53.

Sato T, Vries RG, Snippert HJ, van de Wetering M, Barker N, Stange DE, van Es JH, Abo A, Kujala P, Peters PJ, Clevers H (2009) Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche. Nature 459:262–265PubMedCrossRef

54.

Sato T, van Es JH, Snippert HJ, Stange DE, Vries RG, van den Born M, Barker N, Shroyer NF, van de Wetering M, Clevers H (2011) Paneth cells constitute the niche for Lgr5 stem cells in intestinal crypts. Nature 469:415–418PubMedCrossRef

55.

Kimura H, Sakai K, Arao T, Shimoyama T, Tamura T, Nishio K (2007) Antibody-dependent cellular cytotoxicity of cetuximab against tumor cells with wild-type or mutant epidermal growth factor receptor. Cancer Sci 98:1275–1280PubMedCrossRef

56.

Kawaguchi Y, Kono K, Mimura K, Sugai H, Akaike H, Fujii H (2007) Cetuximab induce antibody-dependent cellular cytotoxicity against EGFR-expressing esophageal squamous cell carcinoma. Int J Cancer 120:781–787PubMedCrossRef

57.

Lievre A, Bachet JB, Le Corre D, Boige V, Landi B, Emile JF, Cote JF, Tomasic G, Penna C, Ducreux M, Rougier P, Penault-Llorca F, Laurent-Puig P (2006) KRAS mutation status is predictive of response to cetuximab therapy in colorectal cancer. Cancer Res 66:3992–3995PubMedCrossRef

58.

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 96:1166–1169PubMedCrossRef

59.

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 19:508–515PubMedCrossRef

60.

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 26:374–379PubMedCrossRef

61.

Karapetis CS, Khambata-Ford S, Jonker DJ, O’Callaghan CJ, Tu D, Tebbutt NC, Simes RJ, Chalchal H, Shapiro JD, Robitaille S, Price TJ, Shepherd L, Au HJ, Langer C, Moore MJ, Zalcberg JR (2008) KRAS mutations and benefit from cetuximab in advanced colorectal cancer. N Engl J Med 359:1757–1765PubMedCrossRef

62.

Allegra CJ, Jessup JM, Somerfield MR, Hamilton SR, Hammond EH, Hayes DF, McAllister PK, Morton RF, Schilsky RL (2009) American Society of Clinical Oncology provisional clinical opinion: testing for KRAS gene mutations in patients with metastatic colorectal carcinoma to predict response to antiepidermal growth factor receptor monoclonal antibody therapy. J Clin Oncol 27:2091–2096PubMedCrossRef

63.

Van Cutsem E, Tejpar S, Vanbeckevoort D, Peeters M, Humblet Y, Gelderblom H, Vermorken JB, Viret F, Glimelius B, Gallerani E, Hendlisz A, Cats A, Moehler M, Sagaert X, Vlassak S, Schlichting M, Ciardiello F (2012) Intrapatient cetuximab dose escalation in metastatic colorectal cancer according to the grade of early skin reactions: the randomized EVEREST study. J Clin Oncol 30:2861–2868PubMedCrossRef

64.

Orditura M, De Vita F, Galizia G, Lieto E, Vecchione L, Vitiello F, Martinelli E, Ciardiello F (2009) Correlation between efficacy and skin rash occurrence following treatment with the epidermal growth factor receptor inhibitor cetuximab: a single institution retrospective analysis. Oncol Rep 21:1023–1028PubMedCrossRef

65.

Tejpar S, Piessevaux H, Claes K, Piront P, Hoenderop JG, Verslype C, Van Cutsem E (2007) Magnesium wasting associated with epidermal-growth-factor receptor-targeting antibodies in colorectal cancer: a prospective study. Lancet Oncol 8:387–394PubMedCrossRef

66.

Costa A, Tejpar S, Prenen H, Van Cutsem E (2011) Hypomagnesaemia and targeted antiepidermal growth factor receptor (EGFR) agents. Target Oncol 6:227–233PubMedCrossRef

67.

Khambata-Ford S, Garrett CR, Meropol NJ, Basik M, Harbison CT, Wu S, Wong TW, Huang X, Takimoto CH, Godwin AK, Tan BR, Krishnamurthi SS, Burris HA III, Poplin EA, Hidalgo M, Baselga J, Clark EA, Mauro DJ (2007) Expression of epiregulin and amphiregulin and K-ras mutation status predict disease control in metastatic colorectal cancer patients treated with cetuximab. J Clin Oncol 25:3230–3237PubMedCrossRef

68.

Jacobs B, De Roock W, Piessevaux H, Van Oirbeek R, Biesmans B, De Schutter J, Fieuws S, Vandesompele J, Peeters M, Van Laethem JL, Humblet Y, Penault-Llorca F, De Hertogh G, Laurent-Puig P, Van Cutsem E, Tejpar S (2009) Amphiregulin and epiregulin mRNA expression in primary tumors predicts outcome in metastatic colorectal cancer treated with cetuximab. J Clin Oncol 27:5068–5074PubMedCrossRef

69.

Tabernero J, Cervantes A, Rivera F, Martinelli E, Rojo F, von Heydebreck A, Macarulla T, Rodriguez-Braun E, Eugenia Vega-Villegas M, Senger S, Ramos FJ, Rosello S, Celik I, Stroh C, Baselga J, Ciardiello F (2010) Pharmacogenomic and pharmacoproteomic studies of cetuximab in metastatic colorectal cancer: biomarker analysis of a phase I dose-escalation study. J Clin Oncol 28:1181–1189PubMedCrossRef

70.

Sobrero AF, Maurel J, Fehrenbacher L, Scheithauer W, Abubakr YA, Lutz MP, Vega-Villegas ME, Eng C, Steinhauer EU, Prausova J, Lenz HJ, Borg C, Middleton G, Kroning H, Luppi G, Kisker O, Zubel A, Langer C, Kopit J, Burris HA III (2008) EPIC: phase III trial of cetuximab plus irinotecan after fluoropyrimidine and oxaliplatin failure in patients with metastatic colorectal cancer. J Clin Oncol 26:2311–2319PubMedCrossRef

71.

Maughan TS, Adams RA, Smith CG, Meade AM, Seymour MT, Wilson RH, Idziaszczyk S, Harris R, Fisher D, Kenny SL, Kay E, Mitchell JK, Madi A, Jasani B, James MD, Bridgewater J, Kennedy MJ, Claes B, Lambrechts D, Kaplan R, Cheadle JP (2011) Addition of cetuximab to oxaliplatin-based first-line combination chemotherapy for treatment of advanced colorectal cancer: results of the randomised phase 3 MRC COIN trial. Lancet 377:2103–2114PubMedCrossRef

72.

Tveit KM, Guren T, Glimelius B, Pfeiffer P, Sorbye H, Pyrhonen S, Sigurdsson F, Kure E, Ikdahl T, Skovlund E, Fokstuen T, Hansen F, Hofsli E, Birkemeyer E, Johnsson A, Starkhammar H, Yilmaz MK, Keldsen N, Erdal AB, Dajani O, Dahl O, Christoffersen T (2012) Phase III trial of cetuximab with continuous or intermittent fluorouracil, leucovorin, and oxaliplatin (Nordic FLOX) versus FLOX alone in first-line treatment of metastatic colorectal cancer: the NORDIC-VII study. J Clin Oncol 30:1755–1762PubMedCrossRef

73.

Yang XD, Jia XC, Corvalan JR, Wang P, Davis CG (2001) Development of ABX-EGF, a fully human anti-EGF receptor monoclonal antibody, for cancer therapy. Crit Rev Oncol Hematol 38:17–23PubMedCrossRef

74.

Foon KA, Yang XD, Weiner LM, Belldegrun AS, Figlin RA, Crawford J, Rowinsky EK, Dutcher JP, Vogelzang NJ, Gollub J, Thompson JA, Schwartz G, Bukowski RM, Roskos LK, Schwab GM (2004) Preclinical and clinical evaluations of ABX-EGF, a fully human antiepidermal growth factor receptor antibody. Int J Radiat Oncol Biol Phys 58:984–990PubMedCrossRef

75.

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 25:1658–1664PubMedCrossRef

76.

Peeters M, Price TJ, Cervantes A, Sobrero AF, Ducreux M, Hotko Y, Andre T, Chan E, Lordick F, Punt CJ, Strickland AH, Wilson G, Ciuleanu TE, Roman L, Van Cutsem E, Tzekova V, Collins S, Oliner KS, Rong A, Gansert J (2010) Randomized phase III study of panitumumab with fluorouracil, leucovorin, and irinotecan (FOLFIRI) compared with FOLFIRI alone as second-line treatment in patients with metastatic colorectal cancer. J Clin Oncol 28:4706–4713PubMedCrossRef

77.

Saltz LB, Meropol NJ, Loehrer PJ Sr, Needle MN, Kopit J, Mayer RJ (2004) Phase II trial of cetuximab in patients with refractory colorectal cancer that expresses the epidermal growth factor receptor. J Clin Oncol 22:1201–1208PubMedCrossRef

78.

Chung KY, Shia J, Kemeny NE, Shah M, Schwartz GK, Tse A, Hamilton A, Pan D, Schrag D, Schwartz L, Klimstra DS, Fridman D, Kelsen DP, Saltz LB (2005) Cetuximab shows activity in colorectal cancer patients with tumors that do not express the epidermal growth factor receptor by immunohistochemistry. J Clin Oncol 23:1803–1810PubMedCrossRef

79.

Hecht J, Mitchell E, Baranda J, Malik I, Richards D, Navale L, D’Avirro P, Amado R (2006) Panitumumab antitumor activity in patients with metastatic colorectal cancer expressing low (1-9 %) or negative (<1 %) levels of epidermal growth factor receptor. J Clin Oncol 18S (abstr 3547).

80.

Licitra L, Storkel S, Kerr KM, Van Cutsem E, Pirker R, Hirsch FR, Vermorken JB, von Hoff A, Esser R, Celik I, Ciardiello F (2012) Predictive value of epidermal growth factor receptor expression for first-line chemotherapy plus cetuximab in patients with head and neck and colorectal cancer: analysis of data from the EXTREME and CRYSTAL studies. Eur J Cancer doi:. doi:10.1016/j.ejca.2012

81.

Barber TD, Vogelstein B, Kinzler KW, Velculescu VE (2004) Somatic mutations of EGFR in colorectal cancers and glioblastomas. N Engl J Med 351:2883PubMedCrossRef

82.

Tsuchihashi Z, Khambata-Ford S, Hanna N, Janne PA (2005) Responsiveness to cetuximab without mutations in EGFR. N Engl J Med 353:208–209PubMedCrossRef

83.

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 6:279–286PubMedCrossRef

84.

Cappuzzo F, Finocchiaro G, Rossi E, Janne PA, Carnaghi C, Calandri C, Bencardino K, Ligorio C, Ciardiello F, Pressiani T, Destro A, Roncalli M, Crino L, Franklin WA, Santoro A, Varella-Garcia M (2008) EGFR FISH assay predicts for response to cetuximab in chemotherapy refractory colorectal cancer patients. Ann Oncol 19:717–723PubMedCrossRef

85.

Personeni N, Fieuws S, Piessevaux H, De Hertogh G, De Schutter J, Biesmans B, De Roock W, Capoen A, Debiec-Rychter M, Van Laethem JL, Peeters M, Humblet Y, Van Cutsem E, Tejpar S (2008) Clinical usefulness of EGFR gene copy number as a predictive marker in colorectal cancer patients treated with cetuximab: a fluorescent in situ hybridization study. Clin Cancer Res 14:5869–5876PubMedCrossRef

86.

Sartore-Bianchi A, Moroni M, Veronese S, Carnaghi C, Bajetta E, Luppi G, Sobrero A, Barone C, Cascinu S, Colucci G, Cortesi E, Nichelatti M, Gambacorta M, Siena S (2007) Epidermal growth factor receptor gene copy number and clinical outcome of metastatic colorectal cancer treated with panitumumab. J Clin Oncol 25:3238–3245PubMedCrossRef

87.

Samowitz WS, Curtin K, Schaffer D, Robertson M, Leppert M, Slattery ML (2000) Relationship of Ki-ras mutations in colon cancers to tumor location, stage, and survival: a population-based study. Cancer Epidemiol Biomarkers Prev 9:1193–1197PubMed

88.

Andreyev HJ, Norman AR, Cunningham D et al (2001) Kirsten ras mutations in patients with colorectal cancer: the 'RASCAL II' study. Br J Cancer 85:692–696PubMedCrossRef

89.

De Roock W, Jonker DJ, Di Nicolantonio F, Sartore-Bianchi A, Tu D, Siena S, Lamba S, Arena S, Frattini M, Piessevaux H, Van Cutsem E, O’Callaghan CJ, Khambata-Ford S, Zalcberg JR, Simes J, Karapetis CS, Bardelli A, Tejpar S (2010) Association of KRAS p G13D mutation with outcome in patients with chemotherapy-refractory metastatic colorectal cancer treated with cetuximab. JAMA 304:1812–1820PubMedCrossRef

90.

Tejpar S, Celik I, Schlichting M, Sartorius U, Bokemeyer C, Van Cutsem E (2012) Association of KRAS G13D tumor mutations with outcome in patients with metastatic colorectal cancer treated with first-line chemotherapy with or without cetuximab. J Clin Oncol 30:3570–3577PubMedCrossRef

91.

Misale S, Yaeger R, Hobor S, Scala E, Janakiraman M, Liska D, Valtorta E, Schiavo R, Buscarino M, Siravegna G, Bencardino K, Cercek A, Chen CT, Veronese S, Zanon C, Sartore-Bianchi A, Gambacorta M, Gallicchio M, Vakiani E, Boscaro V, Medico E, Weiser M, Siena S, Di NF, Solit D, Bardelli A (2012) Emergence of KRAS mutations and acquired resistance to anti-EGFR therapy in colorectal cancer. Nature 486:532–536PubMed

92.

Di Nicolantonio F, Martini M, Molinari F, Sartore-Bianchi A, Arena S, Saletti P, De Dosso S, Mazzucchelli L, Frattini M, Siena S, Bardelli A (2008) Wild-type BRAF is required for response to panitumumab or cetuximab in metastatic colorectal cancer. J Clin Oncol 26:5705–5712PubMedCrossRef

93.

Loupakis F, Ruzzo A, Cremolini C, Vincenzi B, Salvatore L, Santini D, Masi G, Stasi I, Canestrari E, Rulli E, Floriani I, Bencardino K, Galluccio N, Catalano V, Tonini G, Magnani M, Fontanini G, Basolo F, Falcone A, Graziano F (2009) KRAS codon 61, 146 and BRAF mutations predict resistance to cetuximab plus irinotecan in KRAS codon 12 and 13 wild-type metastatic colorectal cancer. Br J Cancer 101:715–721PubMedCrossRef

94.

Laurent-Puig P, Cayre A, Manceau G, Buc E, Bachet JB, Lecomte T, Rougier P, Lievre A, Landi B, Boige V, Ducreux M, Ychou M, Bibeau F, Bouche O, Reid J, Stone S, Penault-Llorca F (2009) Analysis of PTEN, BRAF, and EGFR status in determining benefit from cetuximab therapy in wild-type KRAS metastatic colon cancer. J Clin Oncol 27:5924–5930PubMedCrossRef

95.

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 (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:e15980PubMedCrossRef

96.

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 101:465–472PubMedCrossRef

97.

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 15:3184–3188PubMedCrossRef

98.

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 20:84–90PubMedCrossRef

99.

Sartore-Bianchi A, Martini M, Molinari F, Veronese S, Nichelatti M, Artale S, Di Nicolantonio F, Saletti P, De Dosso S, Mazzucchelli L, Frattini M, Siena S, Bardelli A (2009) PIK3CA mutations in colorectal cancer are associated with clinical resistance to EGFR-targeted monoclonal antibodies. Cancer Res 69:1851–1857PubMedCrossRef

100.

Diaz LA Jr, Williams RT, Wu J, Kinde I, Hecht JR, Berlin J, Allen B, Bozic I, Reiter JG, Nowak MA, Kinzler KW, Oliner KS, Vogelstein B (2012) The molecular evolution of acquired resistance to targeted EGFR blockade in colorectal cancers. Nature 486:537–540PubMed

101.

Montagut C, Dalmases A, Bellosillo B, Crespo M, Pairet S, Iglesias M, Salido M, Gallen M, Marsters S, Tsai SP, Minoche A, Seshagiri S, Serrano S, Himmelbauer H, Bellmunt J, Rovira A, Settleman J, Bosch F, Albanell J (2012) Identification of a mutation in the extracellular domain of the epidermal growth factor receptor conferring cetuximab resistance in colorectal cancer. Nat Med 18:221–223PubMedCrossRef

102.

Chapman PB, Hauschild A, Robert C, Haanen JB, Ascierto P, Larkin J, Dummer R, Garbe C, Testori A, Maio M, Hogg D, Lorigan P, Lebbe C, Jouary T, Schadendorf D, Ribas A, O’Day SJ, Sosman JA, Kirkwood JM, Eggermont AM, Dreno B, Nolop K, Li J, Nelson B, Hou J, Lee RJ, Flaherty KT, McArthur GA (2011) Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med 364:2507–2516PubMedCrossRef

103.

Kopetz S, Desai J, Chan J, Hecht JR, O’Dwyer PJ, Lee RJ, Nolop K, Saltz LB (2010) PLX4032 in metastatic colorectal cancer patients with mutant BRAF tumors. J Clin Oncol 28:15s (abstr 3534).

104.

Prahallad A, Sun C, Huang S, Di Nicolantonio F, Salazar R, Zecchin D, Beijersbergen RL, Bardelli A, Bernards R (2012) Unresponsiveness of colon cancer to BRAF(V600E) inhibition through feedback activation of EGFR. Nature 483:100–103PubMedCrossRef

105.

Yonesaka K, Zejnullahu K, Okamoto I, Satoh T, Cappuzzo F, Souglakos J, Ercan D, Rogers A, Roncalli M, Takeda M, Fujisaka Y, Philips J, Shimizu T, Maenishi O, Cho Y, Sun J, Destro A, Taira K, Takeda K, Okabe T, Swanson J, Itoh H, Takada M, Lifshits E, Okuno K, Engelman JA, Shivdasani RA, Nishio K, Fukuoka M, Varella-Garcia M, Nakagawa K, Janne PA (2011) Activation of ERBB2 signaling causes resistance to the EGFR-directed therapeutic antibody cetuximab. Sci Transl Med 3:99ra86.

106.

Bertotti A, Migliardi G, Galimi F, Sassi F, Torti D, Isella C, Cora D, Di Nicolantonio F, Buscarino M, Petti C, Ribero D, Russolillo N, Muratore A, Massucco P, Pisacane A, Molinaro L, Valtorta E, Sartore-Bianchi A, Risio M, Capussotti L, Gambacorta M, Siena S, Medico E, Sapino A, Marsoni S, Comoglio PM, Bardelli A, Trusolino L (2011) A molecularly annotated platform of patient-derived xenografts ("xenopatients") identifies HER2 as an effective therapeutic target in cetuximab-resistant colorectal cancer. Cancer Discov 1:508–523PubMedCrossRef

107.

Wilson TR, Fridlyand J, Yan Y, Penuel E, Burton L, Chan E, Peng J, Lin E, Wang Y, Sosman J, Ribas A, Li J, Moffat J, Sutherlin DP, Koeppen H, Merchant M, Neve R, Settleman J (2012) Widespread potential for growth-factor-driven resistance to anticancer kinase inhibitors. Nature 487:505–509PubMedCrossRef

108.

Hecht JR, Mitchell E, Chidiac T, Scroggin C, Hagenstad C, Spigel D, Marshall J, Cohn A, McCollum D, Stella P, Deeter R, Shahin S, Amado RG (2009) A randomized phase IIIB trial of chemotherapy, bevacizumab, and panitumumab compared with chemotherapy and bevacizumab alone for metastatic colorectal cancer. J Clin Oncol 27:672–680PubMedCrossRef

109.

Tol J, Koopman M, Cats A, Rodenburg CJ, Creemers GJ, Schrama JG, Erdkamp FL, Vos AH, van Groeningen CJ, Sinnige HA, Richel DJ, Voest EE, Dijkstra JR, Vink-Borger ME, Antonini NF, Mol L, van Krieken JH, Dalesio O, Punt CJ (2009) Chemotherapy, bevacizumab, and cetuximab in metastatic colorectal cancer. N Engl J Med 360:563–572PubMedCrossRef

110.

Schmoll HJ, Van Cutsem E, Stein A, Valentini V, Glimelius B, Haustermans K, Nordlinger B, van de Velde CJ, Balmana J, Regula J, Nagtegaal ID, Beets-Tan RG, Arnold D, Ciardiello F, Hoff P, Kerr D, Kohne CH, Labianca R, Price T, Scheithauer W, Sobrero A, Tabernero J, Aderka D, Barroso S, Bodoky G, Douillard JY, El Ghazaly H, Gallardo J, Garin A, Glynne-Jones R, Jordan K, Meshcheryakov A, Papamichail D, Pfeiffer P, Souglakos I, Turhal S, Cervantes A (2012) ESMO Consensus guidelines for management of patients with colon and rectal cancer. a personalized approach to clinical decision making. Ann Oncol 23:2479–2516PubMedCrossRef

Titel: Role of targeted agents in metastatic colorectal cancer
verfasst von: Hans Prenen
Loredana Vecchione
Eric Van Cutsem
Publikationsdatum: 01.06.2013
Verlag: Springer-Verlag
Erschienen in: Targeted Oncology / Ausgabe 2/2013
Print ISSN: 1776-2596
Elektronische ISSN: 1776-260X
DOI: https://doi.org/10.1007/s11523-013-0281-x

Springer Medizin

Role of targeted agents in metastatic colorectal cancer

Abstract

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Springer Medizin

Abstract

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