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Treatment Options for Patients With Unresectable Colorectal Cancer With Wild-Type KRAS

  • Therapeutic Approaches to Metastatic Colorectal Cancers (E Díaz-Rubio, Section Editor)
  • Published:
Current Colorectal Cancer Reports

Abstract

KRAS mutation has been demonstrated to be an important marker which can be utilized to identify a subset of patients who will not benefit from, and may, in fact, be harmed by, treatment with anti- EGFR agents. The presence of an exon 2 KRAS mutation tells us not to use an anti-EGFR monoclonal antibody. A KRAS wild type result tells us that the option of using an anti-EGFR monoclonal antibody does exist, however it does not compel the use of these antibodies in first-line regimens. How and when to utilize the anti-EGFR agents in the management of patients with KRAS wild type tumors is the subject of this manuscript.

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References

Papers of particular interest published recently, have been highlighted as: • Of importance, •• Of major importance

  1. 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;25:3230–7.

    Article  PubMed  CAS  Google Scholar 

  2. 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. 2008;26:1626–34.

    Article  PubMed  CAS  Google Scholar 

  3. Alberts SR, Sargent DJ, Nair S., et al.: Randomized Phase III Trial of Oxaliplatin, 5-Fluorouracil, and Leucovorin with or without Cetuximab after Curative Resection for Patients with Stage III Colon Cancer, N0147. JAMA, 2012

  4. • Vakiani E, Janakiraman M, Shen R, et al: Comparative Genomic Analysis of Primary Versus Metastatic Colorectal Carcinomas. Journal of Clinical Oncology, 2012. This demonstrates the consistency of KRAS mutational status between the primary and the metastasis, and supports the recommendation not to perform a biopsy of metastatic disease solely to determine KRAS mutational status.

  5. Tournigand C, Louvet C, Quinaux E, et al. FOLFIRI Followed by FOLFOX versus FOLFOX followed by FOLFIRI in Metastic Colorectal Cancer (MCRC): Final Results of a Phase III Study. Proc Am Soc Clin Oncol 20, 2001

  6. Colucci G, Gebbia V, Paoletti G, et al. Phase III randomized trial of FOLFIRI vs FOLFOX4 in the treatment of advanced colorectal cancer: amulticenter study of the Grupo Oncologico Italia Meridionale. J Clin Oncol. 2005;23:4866–75.

    Article  PubMed  CAS  Google Scholar 

  7. Cassidy J, Clarke S, Diaz-Rubio E, et al. Randomized phase III study of capecitabine plus oxaliplatin compared with fluorouracil/folinic acid plus oxaliplatin as first-line therapy for metastatic colorectal cancer. J Clin Oncol. 2008;26:2006–12.

    Article  PubMed  CAS  Google Scholar 

  8. Fuchs CS, Marshall J, Mitchell E, et al. Randomized, controlled trial of irinotecan plus infusional, bolus, or oral fluoropyrimidines in first-line treatment of metastatic colorectal cancer: results from the BICC-C study. J Clin Oncol. 2007;25:4779–86.

    Article  PubMed  CAS  Google Scholar 

  9. Seymour MT, Maughan TS, Ledermann JA, et al. Different strategies of sequential and combination chemotherapy for patients with poor prognosis advanced colorectal cancer (MRC FOCUS): a randomised controlled trial. The Lancet. 2007;370:143–52.

    Article  CAS  Google Scholar 

  10. Koopman M, Antonini NF, Douma J, et al. Sequential versus combination chemotherapy with capecitabine, irinotecan, and oxaliplatin in advanced colorectal cancer (CAIRO): a phase III randomised controlled trial. The Lancet. 2007;370:135–42.

    Article  CAS  Google Scholar 

  11. Saltz L, Rubin, M., Hochster, H., Tchekmeydian, N.S., Waksal, H., Needle, M., LoBuglio, A.: Cetuximab (IMC-C225) Plus Irinotecan (CPT-11) is Active in CPT-11-Refractory Colorectal Cancer (CRC) that Expresses Epidermal Growth Factor Receptor (EGFR). J Clin Oncol 20 (Suppl):abstract #7, 2001

  12. Saltz LB, Meropol NJ, Loehrer Sr PJ, et al. Phase II trial of cetuximab in patients with refractory colorectal cancer that expresses the epidermal growth factor receptor. J Clin Oncol. 2004;22:1201–8.

    Article  PubMed  CAS  Google Scholar 

  13. Cunningham D, Pyrhonen S, James R, et al. Randomised trial of irinotecan plus supportive care versus supportive care alone after fluorouracil failure for patients with metastatic colorectal cancer. Lancet. 1998;352:1413.

    Article  PubMed  CAS  Google Scholar 

  14. Jonker DJ, O'Callaghan CJ, Karapetis CS, et al. Cetuximab for the treatment of colorectal cancer. N Engl J Med. 2007;357:2040–8.

    Article  PubMed  CAS  Google Scholar 

  15. • Karapetis CS, Khambata-Ford S, Jonker DJ, et al: K-ras Mutations and Benefit from Cetuximab in Advanced Colorectal Cancer. N Engl J Med 359:1757-1765, 2008. This demonstrates the substantial clinical benefit of single agent cetuximab in the salvage setting, and shows that it is not necessary to use this agent in the front line in order to obtain a survival benefit.

  16. Van Cutsem E, Kohne C-H, Hitre E, et al. Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med. 2009;360:1408–17.

    Article  PubMed  Google Scholar 

  17. 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. 2009;27:663–71.

    Article  PubMed  CAS  Google Scholar 

  18. Maughan TS, Adams RA, Smith CG, et al. 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. The Lancet. 2012;377:2103–14.

    Article  Google Scholar 

  19. Tveit KM, Guren T, Glimelius B, et al. 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. Journal of Clinical Oncology. 2012;30:1755–62.

    Article  PubMed  CAS  Google Scholar 

  20. Douillard J-Y, 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. Journal of Clinical Oncology. 2010;28:4697–705.

    Article  PubMed  CAS  Google Scholar 

  21. Moosmann N, von Weikersthal LF, Vehling-Kaiser U, et al. 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. Journal of Clinical Oncology. 2011;29:1050–8.

    Article  PubMed  CAS  Google Scholar 

  22. Hurwitz H, Fehrenbacher L, Novotny W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med. 2004;350:2335–42.

    Article  PubMed  CAS  Google Scholar 

  23. Saltz LB, Clarke S, Diaz-Rubio E, et al. Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study. J Clin Oncol. 2008;26:2013–9.

    Article  PubMed  CAS  Google Scholar 

  24. Saltz LB, Lenz H-J, 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. 2007;25:4557–61.

    Article  PubMed  CAS  Google Scholar 

  25. 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. 2009;27:672–80.

    Article  PubMed  CAS  Google Scholar 

  26. Tol J, Koopman M, Cats A, et al. Chemotherapy, bevacizumab, and cetuximab in metastatic colorectal cancer. N Engl J Med. 2009;360:563–72.

    Article  PubMed  CAS  Google Scholar 

  27. •• 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. Journal of Clinical Oncology. 2011;29:2011-9. This trial is the first positive trial of adding cetuximab to FOLFIRI in the first line setting in colorectal cancer. It demonstrates a survival benefit for the addition of cetuximab, however this needs to be viewed in the context of the information in the Karapetis trial referenced above.

  28. Adam R, Wicherts DA, de Haas RJ, et al. Patients with initially unresectable colorectal liver metastases: is there a possibility of cure? J Clin Oncol. 2009;27:1829–35.

    Article  PubMed  Google Scholar 

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Disclosure

L. B. Saltz: consultant (Bristol Myers Squibb, Novartis, Bayer), review activities (Astellas).

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Authors and Affiliations

  1. Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

    Leonard B. Saltz

  2. Weill Medical College of Cornell University, New York, NY, USA

    Leonard B. Saltz

  3. 300 East 66th Street, Room 1049, New York, NY, 10065, USA

    Leonard B. Saltz

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  1. Leonard B. Saltz
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Correspondence to Leonard B. Saltz.

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Saltz, L.B. Treatment Options for Patients With Unresectable Colorectal Cancer With Wild-Type KRAS. Curr Colorectal Cancer Rep 8, 170–176 (2012). https://doi.org/10.1007/s11888-012-0134-5

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  • DOI: https://doi.org/10.1007/s11888-012-0134-5

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