Cetuximab in metastatic colorectal cancer

Expert Review of Anticancer Therapy

Volumn 12, Issue 5, 2012, Pages 555-565

  Broadbridge, Vy Tuong ^a   Karapetis, Cristos S ^b   Price, Timothy Jay ^a  

^a UNIVERSITY OF ADELAIDE   (Australia)

^b FLINDERS MEDICAL CENTRE   (Australia)

Author keywords

cetuximab; EGF receptor inhibitors; metastatic colorectal cancer

Indexed keywords

BEVACIZUMAB; CAPECITABINE; CETUXIMAB; EPIDERMAL GROWTH FACTOR RECEPTOR; FLUOROURACIL; FOLINIC ACID; IRINOTECAN; K RAS PROTEIN; OXALIPLATIN; PANITUMUMAB;

ABDOMINAL PAIN; AIRWAY OBSTRUCTION; ANAPHYLAXIS; ANGIOGENESIS; ANTINEOPLASTIC ACTIVITY; CANCER INHIBITION; CANCER INVASION; COLORECTAL CANCER; DIARRHEA; DRUG CLEARANCE; DRUG EFFICACY; DRUG ELIMINATION; DRUG ERUPTION; DRUG FEVER; DRUG HALF LIFE; DRUG METABOLISM; DRUG POTENTIATION; DRUG RECEPTOR BINDING; DRUG RESPONSE; DRUG SAFETY; DRUG TOLERABILITY; DYSPNEA; FATIGUE; FLUSHING; GASTROINTESTINAL TOXICITY; HEART ARREST; HUMAN; HYPOMAGNESEMIA; HYPOTENSION; LIVER METASTASIS; LIVER RESECTION; LOADING DRUG DOSE; MAXIMUM PLASMA CONCENTRATION; METASTATIC COLORECTAL CANCER; MONOTHERAPY; MUTANT; OVERALL SURVIVAL; PHARMACODYNAMICS; PROGRESSION FREE SURVIVAL; QUALITY OF LIFE; RECOMMENDED DRUG DOSE; REVIEW; RIGOR; SIDE EFFECT; SKIN TOXICITY; URTICARIA; WILD TYPE;

ANTIBODIES, MONOCLONAL; ANTINEOPLASTIC AGENTS; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; CAMPTOTHECIN; COLORECTAL NEOPLASMS; HUMANS; LIVER NEOPLASMS; MUTATION; PROTO-ONCOGENE PROTEINS; RAS PROTEINS; RECEPTOR, EPIDERMAL GROWTH FACTOR;

EID: 84861325349     PISSN: 14737140     EISSN: 17448328     Source Type: Journal    
DOI: 10.1586/era.12.25     Document Type: Review

References (68)

1. Peeters M, Price T, Van Laethem JL. Anti-epidermal growth factor receptor monotherapy in the treatment of metastatic colorectal cancer: where are we today? Oncologist 14, 29-39 (2009).
2. Grothey A, Sargent D, Goldberg RM, Schmoll HJ. 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, 1209-1214 (2004).
3. Tabernero J, Van Cutsem E, Lakomy R et al. Results from VELOUR, a Phase 3 study of aflibercept versus placebo in combination with FOLFIRI for the treatment of patients with previously treated metastatic colorectal cancer. Presented at: The 2011 European Multidisciplinary Cancer Congress (EMCC). Stockholm, Sweden, 23-27 September 2011 (Abstract 6LBA).
4. Grothey, Sobrero AF, Siena A et al. Results of a randomized Phase 3 trial (CORRECT) of regorafenib plus best supportive care (BSC) versus placebo plus BSC in patients with mCRC who have progressed after standard therapies. Presented at: The 2012 Gastrointestinal Cancers Symposium. CA, USA, 19-21 January 2012.
5. Douillard JY, Siena S, Cassidy J et al. 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, 4697-4705 (2010).
6. Peeters M, Price TJ, Cervantes A et al. 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, 4706-4713 (2010).
7. 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. 25, 1658-1664 (2007).
8. Amado RG, Wolf M, Peeters M et al. Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. J. Clin. Oncol. 26, 1626-1634 (2008).
9. Jean GW, Shah SR. Epidermal growth factor receptor antibodies and colorectal cancer: pharmacokinetics and pharmacodynamics. Pharmacotherapy 28(6), 742-754 (2008).
10. 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. 25, 3230-3237 (2007).
11. Lenz HJ. Anti-EGFR mechanism of action: antitumor effect and underlying cause and adverse events. Oncology 20(Suppl. 5), 5-13 (2006).
12. Zouhairi ME, Charabaty A, Pishvaian MJ. Molecularly targeted therapy for metastatic colon cancer: proven treatments and promising new agents. Gastrointest. Cancer Res. 4, 15-21 (2011).
13. Vincenzi B, Santini D, Tonini G. New issues on cetuximab mechanism of action in epidermal growth factor receptor - negative colorectal cancer: the role of vascular endothelial growth factor. J. Clin. Oncol. 20(12), 1957-1958 (2006).
14. Tarbernero J, Pfeiffer P, Cervantes C. Administration of cetuximab every 2 weeks in the treatment of metastatic colorectal cancer: an effective, more convenient alternative to weekly administration. Oncologist 13, 113-119 (2008).
15. Tabernero J, Cervantes A, Martinelli E et al. Optimal dose of cetuximab administered every 2 weeks (q2w): a Phase I pharmacokinetics (PK) and pharmacodynamics (PD) study of weekly (q1w) and q2w schedules in patients (pts) with metastatic colorectal cancer (mCRC). J. Clin. Oncol. 24(18S) (2006) (Abstract 3085).
16. Pfeiffer P, Bjerregaard JK, Qvortrup C et al. Simplification of cetuximab administration: double dose every second week as a 60 min infusion [Abstract]. J. Clin. Oncol. 25(18S) (2007) (Abstract 4133).
17. Delbaldo C, Pierga JY, Dieras V et al. Pharmacokinetic profile of cetuximab (Erbitux) alone and in combination with irinotecan in patients with advanced EGFR-positive adenocarcinoma. Eur. J. Cancer 41, 1739-1745 (2005).
18. Ettlinger DE, Mitterhauser M, Wadsak W et al. In vivo disposition of irinotecan (cpt-11) and its metabolites in combination with the monoclonal antibody cetuximab. Anticancer Res. 26, 1337-1342 (2006).
19. Balin-Gauthier D, Delord JP, Pillaire MJ et al. Cetuximab potentiates oxaliplatin cytotoxic effect through a defect in NER and DNA replication initiation. Br. J. Cancer 98(1), 120-128 (2008).
20. Lievre A, Bachet JB, Boige V et al. KRAS mutations as an independent prognostic factor in patients with advanced colorectal cancer treated with cetuximab. J. Clin. Oncol. 26, 374-379 (2008).
21. Benvenuti S, Sartore-Bianchi A, Di Nicolantonio F et al. Oncogenic activation of the RAS/RAF signalling pathway impairs the response of metastatic colorectal cancers to anti-epidermal growth factor receptor antibody therapies. Cancer Res. 67, 2643-2648 (2007).
22. Di Fiore F, Blanchard F, Charbonnier F et al. Clinical relevance of KRAS mutation detection in metastatic colorectal cancer treated by cetuximab plus chemotherapy. Br. J. Cancer 96, 1166-1169 (2007).
23. De Roock W, Piessevaux H, De Schutter J et al. KRAS wild-type state predicts survival and is associated to early radiological response in metastatic colorectal cancer treated with cetuximab. Ann. Oncol. 19(3), 508-515 (2008).
24. Di Fiore F, Van Cutsem E, Laurent-Puig P et al. Role of KRAS mutation in predicting response, progression-free survival and overall survival in irinotecan-refractory patients treated with cetuximab plus irinotecan for a metastatic colorectal cancer: analysis of 281 individual data from published series. J. Clin. Oncol. 26(15S) (2008) (Abstract 4035).
25. Jonker DJ, O'Callaghan CJ, Karapetis CS et al. Cetuximab for the treatment of colorectal cancer. N. Engl. J. Med. 357(20), 2040-2048 (2007).
26. Karapetis CS, Khambat-Ford S, Jonker DJ et al. K-ras mutations and benefit from cetuximab in advanced colorectal cancer. N. Engl. J. Med. 359(17), 1757-1765 (2008).
27. Monzon FA, Ogino S, Hammond EH et al. The role of KRAS mutation testing in the management of patients with metastatic colorectal cancer. Arch. Pathol. Lab. Med. 133, 1600-1606 (2009).
28. Anderson SM. Laboratory methods for KRAS mutation analysis: laboratory methods for KRAS mutation detection. Expert Rev. Mol. Diagn. 11(6), 635-642 (2011).
29. Tabernero J, Van Cutsem E, Diaz-Rubio E et al. Phase II trial of cetuximab in combination with fluoruracil, leucovorin and oxaliplatin in the first-line treatment of metastatic colorectal cancer. J. Clin. Oncol. 25(33), 5225-5232 (2007).
30. 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. J. Clin. Oncol. 27(5), 663-671 (2009).
31. Bokemeyer C, Bondarenko I, Hartman JT et al. Efficacy according to biomarker status of cetuximab plus FOLFOX-4 as first-line treatment for metastatic colorectal cancer: the OPUS study. Ann. Oncol. 22(7), 1535-1546 (2011).
32. Van Cutsem E, Köhne CH, Hitre E et al. Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N. Engl. J. Med. 360(14), 1408-1417 (2009).
33. 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), by the Nordic Colorectal Cancer Biomodulation Group. Ann. J. Clin. Oncol. 29(Suppl. 4) (2011) (Abstract 365).
34. Maughan T, Adams RA, Smith CG et al. Addition of cetuximab to oxaliplatin-basedfirst-line combination chemotherapy for treatment of advanced colorectal cancer: results for the randomized Phase 3 MRC COIN trial. Lancet 377, 2103-2114 (2011).
35. Van Cutsem E, Kohne CH, Lang I et al. Cetuximab plus irinotecan, fluoruracil, and leucovorin as first-line treatment for metastatic colorectal cancer: updated analysis of overall survival according to tumour KRAS and BRAF mutation status. J. Clin. Oncol. 29(15), 2011-2019 (2011).
36. Sobrero AF, Maurel J, Fehrenbacher L et al. EPIC: Phase III trial of cetuximab plus irinotecan after fluoropyrimidine and oxaliplatin failure in patients with metastatic colorectal cancer. J. Clin. Oncol. 26(14), 2311-2319 (2008).
37. Eng C, Maurel J, Scheithauer W et al. Impact on quality of life of adding cetuximab to irinotecan in patients who have failed prior oxaliplatin-based therapy: the EPIC trial. Proc. Am. Soc. Clin. Oncol. 25, 164s (2007) (Abstract 4003).
38. Langer C, Kopit J, Awad M et al. Analysis of KRAS mutations in patients with metastatic colorectal cancer receiving cetuximab in combination with irinotecan: results from the EPIC trial. Ann. Oncol. 19(Suppl. 8), viii133 (2008).
39. Cunningham D, Humblet Y, Siena S et al. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N. Engl. J. Med. 351(4), 337-345 (2004).
40. Saltz LB, Meropol NJ, Loehrer PJ Sr, Needle MN, Kopit J, Mayer RJ. Phase II trial of cetuximab in patients with refractory colorectal cancer that expresses the epidermal growth factor receptor. J. Clin. Oncol. 22(7), 1201-1208 (2004).
41. Lenz HJ, Van Cutsem E, Khambat-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. 24, 4914-4921 (2006).
42. Vincenzi B, Santini D, Rabitti C et al. Cetuximab and irinotecan as third-line therapy in advanced colorectal cancer patients: a single centre Phase II trial. Br. J. Cancer 94(6), 792-797 (2006).
43. Saltz LB, Lenz HJ, Kindler HL et al. Randomized Phase II trial of cetuximab, bevacizumab and irinotecan compared with cetuximab and bevacizumab alone in irinotecan-refractory colorectal cancer: the BOND-2 study. J. Clin. Oncol. 25(29), 4557-4561 (2007).
44. Tol J, Koopman M, Cats A et al. Chenotherapy, bevacizumab and cetuximab in metastatic colorectal cancer. N. Engl. J. Med. 360(6), 563-572 (2009).
45. Adam R, Aloia T, Lévi F et al. Hepatic resection after rescue cetuximab treatment for colorectal liver metastases previously refractory to conventional systemic therapy. J. Clin. Oncol. 25(29), 4593 (2007).
46. Folprecht G, Gruenberger T, Bechstein et al. Tumour response and secondary respectability of colorectal liver metastases following neoadjuvant chemotherapy with cetuximab: the CELIM randomized Phase 2 trial. Lancet 11, 38-47 (2010).
47. Lenz HJ. Cetuximab in the management of colorectal cancer. Biologics: Targets Ther. 1(2), 77-91 (2007).
48. Tejpar S, Peeters M, Humblet Y et al. Phase I/II study of cetuximab dose-escalation in patients with metastatic colorectal cancer (mCRC) with no or slight skin reactions on cetuximab standard-dose treatment (EVEREST): pharmacokinetic (PK), pharmacodynamic (PD) and efficacy data. J. Clin. Oncol. 25(18S) (2007) (Abstract 4037).
49. Scope A, Agero AL, Dusza SW et al. Randomized double-blind trial of prophylactic oral minocycline and topical tazarotene for cetuximab-associated acne-like eruption. J. Clin. Oncol. 25(34), 5390-5396 (2007).
50. Jatoi A, Rowland K, Sloan JA et al. Tetracycline to prevent epidermal growth factor receptor inhibitor-induced skin rashes: results of a placebo-controlled trial from the North Central Cancer Treatment Group (N03CB). Cancer 113(4), 847-853 (2008).
51. Lacouture ME, Mitchell EP, Piperdi B et al. Skin toxicity evaluation protocol with panitumumab (STEPP), a Phase II, open-label, randomized trial evaluating the impact of a pre-emptive skin treatment regimen on skin toxicities and quality of life in patients with metastatic colorectal cancer. J. Clin. Oncol. 28(8), 135-157 (2010).
52. Fakih MG, Wilding G, Lombardo J. Cetuximab-induced hypomagnesemia in patients with colorectal cancer. Clin. Colorectal Cancer 6, 152-156 (2006).
53. Schrag D, Chung KY, Flombaum C, Saltz L. Cetuximab therapy and symptomatic hypomagnesemia. J. Natl Cancer Inst. 97, 1221-1224 (2005).
54. Vincenzi B, Galluzzo S, Santini D et al. Early magnesium modifications as a surrogate marker of efficacy of cetuximab-based anticancer treatment in KRAS wild-type advanced colorectal cancer patients. Ann. Oncol. 22(5), 1141-1146 (2011).
55. Vickers MM, Karapetis CS, Tu D et al. The influence of hypomagnesemia (hMg) on overall survival (OS) in a Phase III randomized study of cetuximab (CET) plus best supportive care (BSC) versus BSC: NCIC CTG/AGITG CO.17. J. Clin. Oncol. 29S (2011) (Abstract 3601).
56. Hecht JR, Mitchell E, Chidiac T et al. A randomized Phase IIIB trial of chemotherapy, bevacizumab and panitumumab compared with chemotherapy and bevacizumab alone for metastatic colorectal cancer. J. Clin. Oncol. 27(5), 672-680 (2009).
57. Motl S. Bevacizumab in combination chemotherapy for colorectal and other cancers. Am. J. Health Syst. Pharm. 62(10), 1021-1032 (2005).
58. Mittman N, Au HJ, Tu D et al. Prospective cost-effective analysis of cetuximab in metastatic colorectal cancer: evaluation of National Cancer Institute of Canada Clinical Trials Group CO.17 trial. JNCI 101(17), 1182-1192 (2009).
59. Metges J, Raoul J, Achour N et al. PANERB study: panitumumab after cetuximab-based regimen failure. J. Clin. Oncol. 28S (2010) (Abstract 14000).
60. Wadlow RC, Hezel AF, Wolpin BM et al. A single-arm trial of panitumumab in cetuximab-refractory KRAS wild-type colorectal cancer. J. Clin. Oncol. 29(4s) (2011) (Abstract 428).
61. De Roock W, Jonker DJ, Di Nicolantonio F et al. Association of KRAS p.G13D mutation with outcome in patients with chemotherapy-refractory metastatic colorectal cancer treated with cetuximab. JAMA 304(16), 1812 (2010).
62. Peeters M, Douillard JY, Van Cutsem E et al. Evaluation of individual codon 12 and 13 mutant (MT) KRAS alleles as prognostic and predictive biomarkers of response to panitumumab (pmab) in patients with metastatic colorectal cancer (mCRC). Presented at: The 2011 European Multidisciplinary Cancer Congress (EMCC). Stockholm, Sweden, 23-27 September 2011 (Abstract 33LBA).
63. Di Nicolantonio F, Martini M, Molinari F et al. Wild-type BRAF is required for response to panitumumab or cetuximab in metastatic colorectal cancer. J. Clin. Oncol. 26(35), 5705-5712 (2008).
64. Laurent-Puig P, Cayre A, Manceau G et al. Analysis of PTEN, BRAF, and EGFR status in determining benefit from cetuximab therapy in wild-type KRAS metastaticcolon cancer. J. Clin. Oncol. 27(35), 5924 (2009).
65. Bokemeyer C, Kohne C, Roughier P et al. Cetuximab with chemotherapy (CT) as first-line treatment for metastatic colorectal cancer (mCRC): analysis of the CRYSTAL and OPUS studies according to KRAS and BRAF mutation status. J. Clin. Oncol. 28(15s) (2010) (Abstract 3506).
66. Jonker DJ, Karapetis C, Harbison C et al. High epiregulin (EREG) gene expression plus K-ras wild-type (WT) status as predictors of cetuximab benefit in the treatment of advanced colorectal cancer (ACRC): results from the NCIC CTG CO.17 trial - a Phase III trial of cetuximab versus best supportive care (BSC). J. Clin. Oncol. 27(15s) (2009) (Abstract 4016).
67. Jacobs B, De Roock W, Pissevaux H et al. Amphiregulin and epiregulin mRNA expression in primary tumors predicts outcome in metastatic colorectal cancer treated with cetuximab. J. Clin. Oncol. 27(30), 5068-5074 (2009).
68. Stintzing S, Fischer von Weikersthal L, Decker T 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. doi:10.1093/ annonc/mdr571 (2012) (Epub ahead of print).