BRAF testing in advanced colorectal cancer: Is it ready for prime time?

Clinical Advances in Hematology and Oncology

Volumn 8, Issue 6, 2010, Pages 437-444

  Phillips, Brooke ^a   Kalady, Matthew ^b   Kim, Richard ^a  

^a LERNER RESEARCH INSTITUTE   (United States)

^b Clinical Assistant Professor ^*  (United States)

Author keywords

Braf; Cetuximab; Kras; Metastatic colorectal cancer; Panitumumab

Indexed keywords

B RAF KINASE; BEVACIZUMAB; CAPECITABINE; CETUXIMAB; EPIDERMAL GROWTH FACTOR RECEPTOR; FLUOROURACIL; FOLINIC ACID; IRINOTECAN; K RAS PROTEIN; OXALIPLATIN; PANITUMUMAB; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE;

ADVANCED CANCER; CANCER COMBINATION CHEMOTHERAPY; CLINICAL TRIAL; COLORECTAL CANCER; DRUG EFFICACY; HUMAN; INTERMETHOD COMPARISON; METASTASIS; MONOTHERAPY; MUTATIONAL ANALYSIS; NOTE; PROTEIN FUNCTION; TREATMENT OUTCOME; TREATMENT RESPONSE;

ANTINEOPLASTIC AGENTS; CLINICAL TRIALS AS TOPIC; COLORECTAL NEOPLASMS; DRUG RESISTANCE, NEOPLASM; GENETIC TESTING; HUMANS; PROGNOSIS; PROTO-ONCOGENE PROTEINS; PROTO-ONCOGENE PROTEINS B-RAF; RAS PROTEINS; TUMOR MARKERS, BIOLOGICAL;

EID: 77954508565     PISSN: 15430790     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Note

References (71)

1. Amado RG, Wolf M, Peeters M, et al. Wild-type KRAS is required for pani-tumumab efficacy in patients with metastatic colorectal cancer. J Clin Oncol. 2009;26:1626-1634.
2. Benvenuti S, Sartore-Bianchi A, Di Nicolantonio F, et al. Oncogenic activation of the RAS/RAF signaling pathway impairs the response of metastatic colorectal cancers to anti-epidermal growth factor receptor antibody therapies. Cancer Res. 2007;67:2643-2648.
3. Van Cutsem E, Kohne CH, Hitre E, et al. Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med. 2009;360; 1408-1417.
4. Bokemeyer C, Bondarenko I, Makhson A, et al. Fluorouracil, leucovorin, and oxaliplatin with and without cetuximab in the first-line treatment of metastatic colorectal cancer. N Engl J Med. 2009;360:663-671.
5. Karapetis CS, Khambata-Ford S, Jonker DJ, et al. KRAS mutations and benefit from cetuximab in advanced colorectal cancer. N Engl J Med. 2008;359: 1757-1735.
6. Barault L, Veyrie N, Jooste V, et al. Mutations in the RAS-MAPK, PI(3)K (phosphatidylinositol-3-OHkinase) signaling network correlate wit poor survival in a population-based series of colon cancers. Int J Cancer. 2008;122:2255-2259.
7. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines). Available at: www.nccn.org. Accessed: February 11, 2010.
8. Heinemann V, Stintzing S, Kirchner T, Boeck S, Jung A. Clinical relevance of EGFR- and KRAS-status in colorectal cancer patients treated with monoclonal antibodies directed against the EGFR. Cancer Treat Rev. 2009;35:262-271.
9. Raponi M, Winkler H Dracopoli NC. KRAS mutations predict response to EGFR inhibitors. Curr Opin Pharmacol. 2008;8:413-418.
10. Goldstein N, Armin M. Epidermal growth factor receptor immunohisto- chemical reactivity in patients with American Joint Committee on Cancer Stage IV colon adenocarcinoma. Cancer. 2001;92:1331-1346.
11. Cunningham D, Humblet Y, Siena S, et al. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med. 2004;351:337-345.
12. Chung KY, Shia J, Kemeny N, et al. Cetuximab shows activity in colorectal cancer patients with tumors that do not express the epidermal growth factor receptor by immunohistochemistry. J Clin Oncol. 2005;23:1803-1810.
13. Lenz HJ, Van Cutsem E, Khambata-Ford S, et al. Multicenter phase II and translational study of cetuximab in metastatic colorectal carcinoma refractory to irinotecan, oxaliplatin, and fluoropyrimidines. J Clin Oncol. 2006;24:4914-4921.
14. Sartore-Bianchi A, Moroni M, Veronese S, et al. Epidermal growth factor receptor gene copy number and clinical outcome of metastatic colorectal cancer treated with panitumumab. J Clin Oncol. 2007;25:3238-3245.
15. Kranenburg O. The KRAS oncogene: past, present, and future. Biochem Bio-phys Acta. 2005;1756:81-82.
16. Khambata-Ford S, Garrett CR, Meropol NJ, 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: 3230-3237.
17. Yarden Y, Sliwkowski MX. Untangling the ErbB signalling network. Nat Rev Mol Cell Biol. 2001;2:127-137.
18. Poehlmann A, Kuester D, Meyer F, et al. K-RAS mutation detection in colorectal cancer using the Pyrosequencing technique. Pathol Res Pract. 2007;203: 489-497.
19. Di Nicolantonio, Martini M, Molinari F, et al. Wild-type BRAF is required for response to panitumumab or cetuximab in metastatic colorectal cancer. J Clin Oncol. 2008;26:5705-5712.
20. Jimeno A, Messersmith WA, Hirsch FR, et al. KRAS mutations and sensitivity to epidermal growth factor receptor inhibitors in colorectal cancer: practical application of patient selection. J Clin Oncol. 2009;27:1130-1136.
21. Moroni M, Veronese S, Benvenuti S, et al. Gene copy number for epidermal growth factor receptor (EGFR) and clinical response to antiEGFR treatment in colorectal cancer: a cohort study. Lancet Oncol. 2005;6:279-286.
22. Saif MW, Shah M. K-RAS mutations in colorectal cancer: a practice changing discovery. Clin Adv Hematol Oncol. 2009;64:45-53.
23. Van Cutsem E, Peeters M, Siena S, et al. 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. 2007;25:1626-1634.
24. Hecht JR, Mitchell EP, Baranda J, et al. Panitumumab efficacy in patients with metastatic colorectal cancer with low or undetectable levels of epidermal growth factor receptor: final efficacy and K-RAS analysis. Paper presented at: American Society of Clinical Oncology 2008 Gastrointestinal Cancers Symposium (GCS); January 25-27, 2008; Orlando, FL.
25. Douillard J, Siena S, Cassidy J, et al. Randomized phase 3 study of panitu-mumab with FOLFOX4 compared to FOLFOX4 alone as 1st-line treatment for metastatic colorectal cancer: the PRIME trial. EJC Supplements. 2009;7:6
26. Peeters M, Price T, Hotko Y, et al. Randomized phase III study of panitu-mumab with FOLFIRI vs FOLFIRI alone as second-line treatment in patients with metastatic colorectal cancer. EJC Supplements. 2009;7:10.
27. Peeters M, Price T, Hotko Y, et al. Randomized phase III study of panitu-mumab (pmab) with FOLFIRI versus FOLFIRI alone as second-line treatment (tx) in patients (pts) with metastatic colorectal cancer (mCRC): patient-reported outcomes (PRO). Paper presented at: American Society of Clinical Oncology 2010 Gastrointestinal Cancers Symposium (GCS); January 22-24, 2010; Orlando, FL.
28. Souglakos J, Philips J, Wang R, et al. Prognostic and predictive value of common mutations for treatment response and survival in patients with metastatic colorectal cancer. Br J Cancer. 2009;101:465-472.
29. Sartore-Bianchi A, Di Nicolantonio F, Nichelatti M, et al. Multi-determinants analysis of molecular alterations for predicting clinical benefit to EGFR-targeted monoclonal antibodies in colorectal cancer. PLoS ONE. 2009;4:e7287.
30. Hurwitz H, Fehrenbacher L, Novotny W, et al. Bevacizumab plus irinote-can, fluoruracil, and leucovorin for metastatic colorectal cancer. N Engl J Med. 2004;350:2335-2342.
31. Hurwitz HI, Yi J, Ince W, Novotny WF, Rosen O. The clinical benefit of bevacizumab in metastatic colorectal cancer is independent of K-RAS mutation status: analysis of a phase III study of bevacizumab with chemotherapy in previously untreated metastatic colorectal cancer. Oncologist. 2009;14:22-28.
32. Van Cutsem E, Lang I, Folprecht G, et al. Cetuximab plus FOLFIRI in the treatment of metastatic colorectal cancer (mCRC): the influence of KRAS and BRAF biomarkers on outcome: updated data from the CRYSTAL trial. Paper presented at: American Society of Clinical Oncology 2010 Gastrointestinal Cancers Symposium (GCS); January 22-24, 2010; Orlando, FL.
33. Halilovic E, Solit D. Therapeutic strategies for inhibiting oncogenic BRAF signaling. Curr Opin Pharmacol. 2008;8:419-426.
34. Gorden A, Osman I, Gai W, et al. Analysis of BRAF and N-RAS mutation in metastatic melanoma tissues. Cancer Res. 2003;63:3955-3957.
35. Naoki K, Chen TH, Richards WG, et al. Missense mutations of the BRAF gene in human lung adenocarcinoma. Cancer Res. 2002;62:7001-7003.
36. Xu X, Quiros RM, Gattuso P, Ain KB, Prinz RA. High prevalence of BRAF gene mutation in papillary thyroid carcinomas and thyroid tumor cell lines. Cancer Res. 2003;63:4561-4567.
37. Flaherty K. BRAF validation in melanoma. Clin Adv Hematol Oncol. 2010;8:31-34.
38. Lee JW, Yoo NJ, Soung YH, et al. BRAF mutations in non-Hodgkin's lymphoma. Br J Cancer. 2003;89:1958-1960.
39. Davies H, Bignell GR, Cox C, et al. Mutations of the BRAF gene in human cancer. Nature. 2002;417:949-954.
40. Frattini M, Ferrario C, Bressan P, et al. Alternative mutations of BRAF, RET and NTRK1 are associated with similar but distinct gene expression patterns in papillary thyroid cancer. Oncogene. 2004;23:7436-7440.
41. Sanchez JA, Krumroy L, Plummer S, et al. Genetic and epigenetic classifications define clinical phenotypes and determine patient outcomes in colorectal cancer. Br J Surg. 2009;96:1196-1204.
42. Kalady M, Sanchez J, Manilich E, Hammel J, Casey G, Church JM. Divergent oncogenic changes influence survival differences between colon and rectal adenocarcinomas. Dis Colon Rectum. 2009;52:1039-1045.
43. Loupakis F, Ruzzo A, Cremolini C, et al. 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. 2009;101:715-721.
44. Tol J, Nagtegaal ID, Punt CJ. BRAF mutation in metastatic colorectal carcinoma. N Engl J Med. 2009;361:98-99.
45. Tol J, Koopman M, Cats A, et al. Chemotherapy, bevacizumab, and cetux-imab in metastatic colorectal cancer. N Engl J Med. 2009;360:563-572.
46. Kohne C, Rougier P, Stroh C, Schlichting M, Bokemeyer C, Van Cutsem E. Cetuximab with chemotherapy as first-line treatment for metastatic colorectal cancer: a meta-analysis of the CRYSTAL and OPUS studies according to KRAS and BRAF mutation status. Paper presented at: American Society of Clinical Oncology 2010 Gastrointestinal Cancers Symposium (GCS); January 22-24, 2010; Orlando, FL.
47. Van Cutsem E, Labianca R, Bodoky G, et al. Randomized phase III trial comparing biweekly infusional fluorouracil/leucovorin alone or with irinotecan in the adjuvant treatment of stage III colon cancer: PETACC-3. J Clin Oncol. 2009;27:3117-3125.
48. Roth A, Tejpar S, Delorenzi M, et al. 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.
49. Ogino S, Nosho K, Kirkner GJ, et al. CpG island methylator phenotype, microsatellite instability, BRAF mutation and clinical outcome in colon cancer. Gut. 2009;58:90-96.
50. Samowitz WS, Sweeney C, Herrick J, et al. Poor survival associated with the BRAF V600E mutation in microsatellite-stable colon cancers. Cancer Res. 2005;65:6063-6069.
51. Samowitz WS, Albertsen H, Sweeney C, et al. Association of smoking, CpG island methylator phenotype, and V600E BRAF mutations in colon cancer. J Natl Cancer Inst. 2006;98:1731-1738.
52. Weisenberger DJ, Siegmund KD, Campan M, et al. CpG island methylator phenotype in colorectal cancer. Nat Genet. 2006;38:787-793.
53. Brown P, Levis M, Mclntyre E, et al. Combinations of the FLT3 inhibitor CEP-701 and chemotherapy synergistically kill infant and childhood MLL-rearranged ALL cells in a sequence-dependent manner. Leukemia. 2006;20:1368-1376.
54. Knapper S, Burnett AK, Littlewood T, et al. A phase 2 trial of the FLT3 inhibitor lestaurtinib (CEP701) as first-line treatment for older patients with acute myeloid leukemia not considered fit for intensive chemotherapy. Blood. 2006;108:3262-3270.
55. Levis M, Ravandi F, Wang ES, et al. Results from a randomized trial of salvage chemotherapy followed by lestaurtinib for FLT3 mutant AML patients in first relapse. Blood. 2009;114:325. Abstract 788.
56. Sato T, Knapper S, Burnett AK, et al. Increased plasma FLT3 ligand levels following chemotherapy may interfere with the clinical efficacy of FLT3 inhibitors. Blood. 2009;114:387. Abstract 937.
57. DeAngelo DJ, Stone RM, Heaney ML, et al. Phase I results with tanduti-nib (MLN518), a novel FLT3 antagonist, in patients with acute myelogenous leukemia or high-risk myelodysplastic syndrome: safety, pharmacokinetics, and pharmacodynamics. Blood. 2006;108:3674-3681.
58. Schittenhelm MM, Kampa KM, Yee KW, Heinrich MC. The FLT3 inhibitor Tandutinib (formerly MLN518) has sequence-independent synergistic effects with cytarabine and daunorubicin. Cell Cycle. 2009;8:2621-2630.
59. Cheng Y, Paz K. Tandutinib, an oral, small-molecular inhibitor of FLT3 for the treatment of AML and other cancer indications. IDrugs. 2008;11:46-56.
60. Zarrinkar PP, Gunawardane RN, Cramer MD, et al. AC220 is a uniquely potent and selective inhibitor of FLT3 for the treatment of acute myeloid leukemia (AML). Blood. 2009;114:2984-2992.
61. Chao Q, Sprankle KG, Grotzfeld RM, et al. Identification of N-(5-tert-butyl-isoxazol-3-yl)-N'-{4-[7-(2-morpholin-4-yl-ethoxy)imidazo{2,1-b] [1,3] benzothiazol-2-yl]phenyl}urea dihydrochloride (AC220), a uniquely potent, selective, and efficacious FMS-like tyrosine kinase-3 (FLT3) inhibitor. J Med Chem. 2009;52:7808-7816.
62. James J, Pratz K, Stone A, et al. Clinical pharmacokinetics and FLT3 phos-phorylation of AC220, a highly potent and selective inhibitor of FLT3. Blood. 2008;112. Abstract 2637.
63. Brigham D, Belli BA, Breider M, et al. AC220, a FLT3 inhibitor, increases survival in two genotypically distinct FLT3-ITD models of acute myeloid leukemia and provides sustained protection following chronic administration. Blood. 2009;114:810. Abstract 2053.
64. Belli BA, Dao A, Bhagwat S, et al. AC220, a potent and specific FLT3 inhibitor, enhances the cytotoxic effects of chemotherapeutic agents in cell culture and in mouse tumor xenografts. Blood. 2009;114:810. Abstract 2052.
65. Shiotsu Y, Kiyoi H, Ishikawa Y, et al. KW-2449, a novel multi-kinase inhibitor, suppresses the growth of leukemia cells with FLT3 mutations or T315I-mutated BCR/ABL translocation. Blood. 2009;114:1607-1617.
66. Ikezoe T, Yang J, Nishioka C, et al. A novel treatment strategy targeting Aurora kinases in acute myelogenous leukemia. Mol Cancer Ther. 2007;6:1851-1857.
67. Pratz KW, Cortes J, Roboz GJ, et al. A pharmacodynamic study of the FLT3 inhibitor KW-2449 yields insight into the basis for clinical response. Blood. 2009;113:3938-3946.
68. Pratz KW, Stine A, Karp J, et al. Optimizing the dose and schedule of KW-2449, FLT3/Aurora inhibitor, through analysis of in vivo target inhibition. J Clin Oncol. 2008;26:15s. Abstract 7069.
69. Cortes J, Roboz GJ, Kantarjian HM, et al. A phase I dose escalation study of KW-2449, an oral multi-kinase inhibitor against FLT3, Abl, FGFR1 and Aurora in patients with relapsed/refractory AML, ALL and MDS or resistant/intolerant CML. Blood. 2008;112. Abstract 2967.
70. Pemmaraju N, Kantarjian HM, Ravandi F, et al. Flt3 inhibitor therapy for patients with myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML): impact on survival according to FLT3 status. Blood. 2009;114:424. Abstract 1026.
71. Jin G, Matsushita H, Asai S, et al. FLT3-ITD induces ara-C resistance in myeloid leukemic cells through the repression of the ENT1 expression. Biochem Biophys Res Commun. 2009;390:1001-1006.