Impact of the specific mutation in KRAS codon 12 mutated tumors on treatment efficacy in patients with metastatic colorectal cancer receiving cetuximab-based first-line therapy: A pooled analysis of three trials

Oncology (Switzerland)

Volumn 83, Issue 5, 2012, Pages 241-247

  Modest, Dominik P ^a   Brodowicz, Thomas ^c   Stintzing, Sebastian ^a   Jung, Andreas ^b   Neumann, Jens ^b   Laubender, Ruediger P ^b   Ocvirk, Janja ^c,d   Kurteva, Galina ^c,e   Papai, Zsuzsanna ^c,f   Knittelfelder, Regina ^c   Kirchner, Thomas ^b   Heinemann, Volker ^a   Zielinski, Christoph C ^c  

^a LUDWIG MAXIMILIANS UNIVERSITY   (Germany)

^b UNIVERSITY OF MUNICH   (Germany)

^c MEDICAL UNIVERSITY OF VIENNA   (Austria)

^d INSTITUTE OF ONCOLOGY   (Slovenia)

^e National Oncology Center Bulgaria   (Bulgaria)

^f AEK Onkologiai Osztaly   (Hungary)

Author keywords

Anti epidermal growth factor receptor; Cetuximab; Codon 12; KRAS mutation; Metastatic colorectal cancer

Indexed keywords

CAPECITABINE; CETUXIMAB; FLUOROURACIL; FOLINIC ACID; IRINOTECAN; OXALIPLATIN;

ADULT; AGED; ARTICLE; CANCER CHEMOTHERAPY; CANCER SURVIVAL; CODON; COLORECTAL CANCER; DRUG EFFICACY; ELECTROCORTICOGRAPHY; FEMALE; GENE MUTATION; HUMAN; HUMAN TISSUE; LIVER METASTASIS; LUNG METASTASIS; MAJOR CLINICAL STUDY; MALE; ONCOGENE K RAS; OVERALL SURVIVAL; PERITONEUM METASTASIS; PRIMARY TUMOR; PRIORITY JOURNAL;

ADULT; AGED; AGED, 80 AND OVER; ANTIBODIES, MONOCLONAL; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; CAMPTOTHECIN; CODON; COLORECTAL NEOPLASMS; DEOXYCYTIDINE; DRUG ADMINISTRATION SCHEDULE; FEMALE; FLUOROURACIL; GERMANY; HUMANS; LEUCOVORIN; MALE; MIDDLE AGED; MULTICENTER STUDIES AS TOPIC; MUTATION; ODDS RATIO; ORGANOPLATINUM COMPOUNDS; PROGNOSIS; PROTO-ONCOGENE PROTEINS; RANDOMIZED CONTROLLED TRIALS AS TOPIC; RAS PROTEINS; TREATMENT OUTCOME;

EID: 84865579878     PISSN: 00302414     EISSN: 14230232     Source Type: Journal    
DOI: 10.1159/000339534     Document Type: Article

References (34)

1. Heinemann V, Stintzing S, Kirchner T, Boeck S, Jung A: Clinical relevance of EGFRand KRAS-status in colorectal cancer patients treated with monoclonal antibodies directed against the EGFR. Cancer Treat Rev 2009; 35: 262-271.
2. Khosravi-Far R, Der CJ: The Ras signal transduction pathway. Cancer Metastasis Rev 1994; 13: 67-89.
3. Bos JL, Fearon ER, Hamilton SR, Verlaan-de Vries M, van Boom JH, van der Eb AJ, Vogelstein B: Prevalence of ras gene mutations in human colorectal cancers. Nature 1987; 327: 293-297.
4. Boughdady IS, Kinsella AR, Haboubi NY, Schofield PF: K-ras gene mutations in adenomas and carcinomas of the colon. Surg Oncol 1992; 1: 275-282.
5. Neumann J, Zeindl-Eberhart E, Kirchner T, Jung A: Frequency and type of KRAS mutations in routine diagnostic analysis of metastatic colorectal cancer. Pathol Res Pract 2009; 205: 858-862.
6. Finkelstein SD, Sayegh R, Christensen S, Swalsky PA: Genotypic classification of colorectal adenocarcinoma. Biologic behavior correlates with K-ras-2 mutation type. Cancer 1993; 71: 3827-3838.
7. Bazan V, Migliavacca M, Zanna I, Tubiolo C, Grassi N, Latteri MA, La Farina M, Albanese I, Dardanoni G, Salerno S, Tomasino RM, Labianca R, Gebbia N, Russo A: Specific codon 13 K-ras mutations are predictive of clinical outcome in colorectal cancer patients, whereas codon 12 K-ras mutations are associated with mucinous histotype. Ann Oncol 2002; 13: 1438-1446.
8. Cerottini JP, Caplin S, Saraga E, Givel JC, Benhattar J: The type of K-ras mutation determines prognosis in colorectal cancer. Am J Surg 1998; 175: 198-202.
9. Allegra CJ, Jessup JM, Somerfield MR, Hamilton SR, Hammond EH, Hayes DF, McAllister PK, Morton RF, Schilsky RL: American Society of Clinical Oncology provisional clinical opinion: testing for KRAS gene mutations in patients with metastatic colorectal carcinoma to predict response to anti-epidermal growth factor receptor monoclonal antibody therapy. J Clin Oncol 2009; 27: 2091-2096.
10. Van Cutsem E, Köhne CH, Hitre E, Zaluski J, Chang Chien CR, Makhson A, D'Haens G, Pintér T, Lim R, Bodoky G, Roh JK, Folprecht G, Ruff P, Stroh C, Tejpar S, Schlichting M, Nippgen J, Rougier P: Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med 2009; 360: 1408-1417.
11. Bokemeyer C, Bondarenko I, Hartmann JT, de Braud F, Schuch G, Zubel A, Celik I, Schlichting M, Koralewski P: Efficacy according to biomarker status of cetuximab plus FOLFOX-4 as first-line treatment for metastatic colorectal cancer: the OPUS study. Ann Oncol 2011; 22: 1535-1546.
12. Jonker DJ, O'Callaghan CJ, Karapetis CS, Zalcberg JR, Tu D, Au HJ, Berry SR, Krahn M, Price T, Simes RJ, Tebbutt NC, van Hazel G, Wierzbicki R, Langer C, Moore MJ: Cetuximab for the treatment of colorectal cancer. N Engl J Med 2007; 357: 2040-2048.
13. 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: K-ras mutations and benefit from cetuximab in advanced colorectal cancer. N Engl J Med 2008; 359: 1757-1765.
14. 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, MRC COIN Trial Investigators: Addition of cetuximab to oxaliplatinbased first-line combination chemotherapy for treatment of advanced colorectal cancer: results of the randomised phase 3 MRC COIN trial. Lancet 2011; 377: 2103-2114.
15. Moosmann N, von Weikersthal LF, Vehling-Kaiser U, Stauch M, Hass HG, Dietzfelbinger H, Oruzio D, Klein S, Zellmann K, Decker T, Schulze M, Abenhardt W, Puchtler G, Kappauf H, Mittermüller J, Haberl C, Schalhorn A, Jung A, Stintzing S, Heinemann V: Cetuximab plus capecitabine and irinotecan compared with cetuximab plus capecitabine and oxaliplatin as first-line treatment for patients with metastatic colorectal cancer: AIO KRK-0104-a randomized trial of the German AIO CRC Study Group. J Clin Oncol 2011; 29: 1050-1058.
16. Tveit K, Guren T, Glimelius B, et al: Randomized phase III study of 5-fluorouracil/ folinate/oxaliplatin given continuously or intermittently with or without cetuximab, as first-line treatment of metastatic colorectal cancer: the NORDIC VII Study (NCT00145314) (abstract LBA20). Ann Oncol 2010; 21(suppl 8):9.
17. Douillard JY, Siena S, Cassidy J, Tabernero J, Burkes R, Barugel M, Humblet Y, Bodoky G, Cunningham D, Jassem J, Rivera F, Kocákova I, Ruff P, B?asi?ska-Morawiec M, Šmakal M, Canon JL, Rother M, Oliner KS, Wolf M: 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 2010; 28: 4697-4705.
18. Modest DP, Jung A, Moosmann N, Laubender RP, Giessen C, Schulz C, Haas M, Neumann J, Boeck S, Kirchner T, Heinemann V, Stintzing S: The influence of KRAS and BRAF mutations on the efficacy of cetuximab-based first-line therapy of metastatic colorectal cancer: an analysis of the AIO KRK-0104-trial. Int J Cancer 2011, Epub ahead of print.
19. 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: Association of KRAS p.G13D mutation with outcome in patients with chemotherapy-refractory metastatic colorectal cancer treated with cetuximab. JAMA 2010; 304: 1812-1820.
20. Samowitz WS, Curtin K, Schaffer D, Robertson M, Leppert M, Slattery ML: Relationship of Ki-ras mutations in colon cancers to tumor location, stage, and survival: a population-based study. Cancer Epidemiol Biomarkers Prev 2000; 9: 1193-1197.
21. Andreyev HJ, Norman AR, Cunningham D, Oates J, Dix BR, Iacopetta BJ, Young J, Walsh T, Ward R, Hawkins N, Beranek M, Jandik P, Benamouzig R, Jullian E, Laurent-Puig P, Olschwang S, Muller O, Hoffmann I, Rabes HM, Zietz C, Troungos C, Valavanis C, Yuen ST, Ho JW, Croke CT, O'Donoghue DP, Giaretti W, Rapallo A, Russo A, Bazan V, Tanaka M, Omura K, Azuma T, Ohkusa T, Fujimori T, Ono Y, Pauly M, Faber C, Glaesener R, de Goeij AF, Arends JW, Andersen SN, Lövig T, Breivik J, Gaudernack G, Clausen OP, De Angelis PD, Meling GI, Rognum TO, Smith R, Goh HS, Font A, Rosell R, Sun XF, Zhang H, Benhattar J, Losi L, Lee JQ, Wang ST, Clarke PA, Bell S, Quirke P, Bubb VJ, Piris J, Cruickshank NR, Morton D, Fox JC, Al-Mulla F, Lees N, Hall CN, Snary D, Wilkinson K, Dillon D, Costa J, Pricolo VE, Finkelstein SD, Thebo JS, Senagore AJ, Halter SA, Wadler S, Malik S, Krtolica K, Urosevic N: Kirsten ras mutations in patients with colorectal cancer: the 'RASCAL II' study. Br J Cancer 2001; 85: 692-696.
22. Lamy PJ, Montels F, Servanton AC, Ychou M, Crapez E: Diagnostic of KRAS gene mutations in colorectal cancer: evaluation of direct sequencing, pyrosequencing and allele specific amplification (abstract 1322). ECCO 15 and 34th ESMO Multidisc Congr, Berlin, 2009.
23. Juan T, Suggs S, Wolf M, Sarosi I, Freeman D, Oliner K, Bakkar A, Patterson SD: A comparatibility study of 4 commercial KRAS tests (abstract 1811). Am Assoc Cancer Res Annu Meet, San Diego, 2008.
24. Stintzing S, Fischer von Weikersthal L, Decker T, Vehling-Kaiser U, Jäger E, Heintges T, Stoll C, Giessen C, Modest DP, Neumann J, Jung A, Kirchner T, Scheithauer W, Heinemann V, et al: FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer-subgroup analysis of patients with KRAS: mutated tumours in the randomised German AIO study KRK-0306. Ann Oncol 2012, Epub ahead of print.
25. Ocvirk J, Brodowicz T, Wrba F, Ciuleanu TE, Kurteva G, Beslija S, Koza I, Pápai Z, Messinger D, Yilmaz U, Faluhelyi Z, Yalcin S, Papamichael D, Wenczl M, Mrsic-Krmpotic Z, Shacham-Shmueli E, Vrbanec D, Esser R, Scheithauer W, Zielinski CC: Cetuximab plus FOLFOX6 or FOLFIRI in metastatic colorectal cancer: CECOG trial. World J Gastroenterol 2010; 16: 3133-3143.
26. Tournigand C, André 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: FOLFIRI followed by FOLFOX6 or the reverse sequence in advanced colorectal cancer: a randomized GERCOR study. J Clin Oncol 2004; 22: 229-237.
27. Roth AD, Tejpar S, Delorenzi M, Yan P, Fiocca R, Klingbiel D, Dietrich D, Biesmans B, Bodoky G, Barone C, Aranda E, Nordlinger B, Cisar L, Labianca R, Cunningham D, Van Cutsem E, Bosman F: Prognostic role of KRAS and BRAF in stage II and III resected colon cancer: results of the translational study on the PETACC-3, EORTC 40993, SAKK 60-00 trial. J Clin Oncol 2010; 28: 466-474.
28. Scheffzek K, Ahmadian MR, Wittinghofer A: GTPase-activating proteins: helping hands to complement an active site. Trends Biochem Sci 1998; 23: 257-262.
29. 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: Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. J Clin Oncol 2008; 26: 1626-1634.
30. Cappuzzo F, Varella-Garcia M, Finocchiaro G, Skokan M, Gajapathy S, Carnaghi C, Rimassa L, Rossi E, Ligorio C, Di Tommaso L, Holmes AJ, Toschi L, Tallini G, Destro A, Roncalli M, Santoro A, Jänne PA: Primary resistance to cetuximab therapy in EGFR FISH-positive colorectal cancer patients. Br J Cancer 2008; 99: 83-99.
31. Frattini M, Saletti P, Romagnani E, Martin V, Molinari F, Ghisletta M, Camponovo A, Etienne LL, Cavalli F, Mazzucchelli L: PTEN loss of expression predicts cetuximab efficacy in metastatic colorectal cancer patients. Br J Cancer 2007; 97: 1139-1145.
32. 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 3rd, Poplin EA, Hidalgo M, Baselga J, Clark EA, Mauro DJ: 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: 3230-3237.
33. Lièvre A, Bachet JB, Le Corre D, Boige V, Landi B, Emile JF, Côté JF, Tomasic G, Penna C, Ducreux M, Rougier P, Penault-Llorca F, Laurent-Puig P: KRAS mutation status is predictive of response to cetuximab therapy in colorectal cancer. Cancer Res 2006; 66: 3992-3995.
34. Peeters M, Douillard YI, van Cutsem E, Siena S, Zhang K, Williams R, Wiezorek J: Evaluation of individual codon 12 and 13 mutant KRAS alleles as prognostic and predictive biomarkers of response to panitumumabin patients with metastatic colorectal cancer (mCRC). EJC 2011; 47(suppl 2):33LBA.