Molecular Diagnosis & Therapy

, Volume 16, Issue 5, pp 317–322 | Cite as

Cetuximab

A Guide to Its Use in Combination with FOLFIRI in the First-Line Treatment of Metastatic Colorectal Cancer in the USA
Adis Drug Clinical Q&A

Abstract

Cetuximab (Erbitux®) is a monoclonal antibody that targets the epidermal growth factor receptor (EGFR). In the USA, the approval of cetuximab has been recently expanded to include the first-line treatment of patients with KRAS mutation-negative (wild-type), EGFR-expressing, metastatic colorectal cancer (mCRC) when used in combination with FOLFIRI (irinotecan, fluorouracil, leucovorin [folinic acid]). The addition of cetuximab to first-line treatment with FOLFIRI improved progression-free survival, overall survival, and objective response rates relative to treatment with FOLFIRI alone in patients with EGFR-expressing mCRC with KRAS wild-type tumors. Therefore, cetuximab plus FOLFIRI is a useful biomarker-directed option in the first-line treatment of this patient population.

References

  1. 1.
    McRee AJ, Goldberg RM. Optimal management of metastatic colorectal cancer: current status. Drugs. 2011;71(7):869–84.PubMedCrossRefGoogle Scholar
  2. 2.
    Van Cutsem E, Geboes K. The multidisciplinary management of gastrointestinal cancer: the integration of cytotoxics and biologicals in the treatment of metastatic colorectal cancer. Best Pract Res Clin Gastroenterol. 2007;21(6):1089–108.PubMedCrossRefGoogle Scholar
  3. 3.
    Shankaran V, Wisinski KB, Mulcahy MF, et al. The role of molecular markers in predicting response to therapy in patients with colorectal cancer. Mol Diagn Ther. 2008;12(2):87–98.PubMedCrossRefGoogle Scholar
  4. 4.
    Ciavarella S, Milano A, Dammacco F, et al. Targeted therapies in cancer. Biodrugs. 2010;24(2):77–88.PubMedCrossRefGoogle Scholar
  5. 5.
    Porebska I, Harlozinska A, Bojarowski T. Expression of the tyrosine kinase activity growth factor receptors (EGFR, ERB B2, ERB B3) in colorectal adenocarcinomas and adenomas. Tumour Biol. 2000;21(2):105–15.PubMedCrossRefGoogle Scholar
  6. 6.
    Moosmann N, Heinemann V. Cetuximab in the treatment of metastatic colorectal cancer. Expert Opin Biol Ther. 2007;7(2):243–56.PubMedCrossRefGoogle Scholar
  7. 7.
    Brand TM, Wheeler DL. KRAS mutant colorectal tumors: past and present. Small GTPases. 2012;3(1):34–9.PubMedCrossRefGoogle Scholar
  8. 8.
    Erbitux® (cetuximab): US prescribing information. Princeton: ImClone LLC, a wholly-owned subsidiary of Eli Lilly and Company and Bristol-Myers Squibb Company; 2012.Google Scholar
  9. 9.
    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. 2012;23(7):1693–9.PubMedCrossRefGoogle Scholar
  10. 10.
    Van Cutsem E, Köhne C-H, Láng I, et al. 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. 2011;29(15):2011–9.PubMedCrossRefGoogle Scholar
  11. 11.
    Jonker DJ, O’Callaghan CJ, Karapetis CS, et al. Cetuximab for the treatment of colorectal cancer. N Engl J Med. 2007;357(20):2040–8.PubMedCrossRefGoogle Scholar
  12. 12.
    National Comprehensive Cancer Network (NCCN). NCCN clinical practice guidelines in oncology (NCCN guidelines®): colon cancer. Version 3.2012. Fort Washington: National Comprehensive Cancer Network; 2012.Google Scholar
  13. 13.
    National Comprehensive Cancer Network (NCCN). NCCN clinical practice guidelines in oncology (NCCN guidelines®): rectal cancer. Version 3.2012. Fort Washington: National Comprehensive Cancer Network; 2012.Google Scholar
  14. 14.
    Raoul JL, Van Laethem JL, Peeters M, et al. Cetuximab in combination with irinotecan/5-fluorouracil/folinic acid (FOLFIRI) in the initial treatment of metastatic colorectal cancer: a multicentre two-part phase I/II study. BMC Cancer. 2009;9:112.PubMedCrossRefGoogle Scholar
  15. 15.
    Van Cutsem E, Köhne C-H, Hitre E, et al. Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med. 2009;360(14):1408–17.PubMedCrossRefGoogle Scholar
  16. 16.
    Oldenhuis CN, Oosting SF, Gietema JA, et al. Prognostic versus predictive value of biomarkers in oncology. Eur J Cancer. 2008;44(7):946–53.PubMedCrossRefGoogle Scholar
  17. 17.
    Blick SKA, Scott LJ. Cetuximab: a review of its use in squamous cell carcinoma of the head and neck and metastatic colorectal cancer. Drugs. 2007;67(17):2585–607.PubMedCrossRefGoogle Scholar
  18. 18.
    Vijayaraghavan A, Efrusy MB, Göke B, et al. Cost-effectiveness of KRAS testing in metastatic colorectal cancer patients in the United States and Germany. Int J Cancer. 2012;131(2):438–45.PubMedCrossRefGoogle Scholar
  19. 19.
    Tejpar S, Celik I, Schlichting M, et al. 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 (Epub 2012 Jun 25).Google Scholar
  20. 20.
    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. 2010;304(16):1812–20.PubMedCrossRefGoogle Scholar
  21. 21.
    Ulivi P, Capelli L, Valgiusti M, et al. Predictive role of multiple gene alterations in response to cetuximab in metastatic colorectal cancer: a single center study. J Transl Med. 2012;10:87.PubMedCrossRefGoogle Scholar
  22. 22.
    Custodio A, Feliu J. Prognostic and predictive biomarkers for epidermal growth factor receptor-targeted therapy in colorectal cancer: beyond KRAS mutations. Crit Rev Oncol Hematol (Epub 2012 May 28).Google Scholar
  23. 23.
    Mekenkamp LJ, Tol J, Dijkstra JR, et al. Beyond KRAS mutation status: influence of KRAS copy number status and microRNAs on clinical outcome to cetuximab in metastatic colorectal cancer patients. BMC Cancer. 2012;12(1):292.PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2012

Authors and Affiliations

  1. 1.Adis41 Centorian DriveAucklandNew Zealand

Personalised recommendations