Advertisement

International Journal of Colorectal Disease

, Volume 27, Issue 8, pp 997–1004 | Cite as

Resectability and outcome with anti-EGFR agents in patients with KRAS wild-type colorectal liver-limited metastases: a meta-analysis

  • F. Petrelli
  • S. Barni
  • Anti-EGFR agents for liver metastases
Review

Abstract

Background

Cetuximab (C) and panitumumab (P) increase response rate and survival in KRAS wild-type metastatic colorectal cancer (mCRC). We performed a meta-analysis of randomised controlled trials (RCTs) to assess their effect on overall response rate (ORR), the rate of radical resection (R0) and survival in patients with liver-limited initially unresectable mCRC.

Materials and methods

We searched MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials for RCTs comparing first-line chemotherapy plus or minus C or P and reporting data in patients with KRAS wild-type, unresectable liver-limited mCRC. Relative risks (RRs) with 95% confidence interval were calculated. Meta-analysis of hazard ratios (HRs) for progression-free and overall survival (PFS and OS) was also performed.

Results

Four RCTs involving 484 KRAS wild-type patients were included. Compared to chemotherapy alone, the addition of C or P significantly increased the ORR (RR 1.67, p = 0.0001), the R0 resection rate from 11% to 18% (RR 1.59, p = 0.04) and PFS (HR 0.68, p = 0.002), but not OS (p = 0.42).

Conclusions

The addition of C and P increased the R0 resection rate by 60% and reduced the risk of progression by 32% in patients with mCRC and unresectable liver-limited disease. This combination represents one of the preferred choices as conversion therapy in KRAS wild-type patients with unresectable liver metastases.

Keywords

Cetuximab Panitumumab Liver metastases Colorectal cancer KRAS wild type 

Notes

Conflict of interest

All authors disclose any actual or potential conflict of interest including any financial, personal or other relationships with other people or organizations which could inappropriately influence (bias) their work.

References

  1. 1.
    Adam R, Delvart V, Pascal G, Valeanu A, Castaing D, Azoulay D, Giacchetti S, Paule B, Kunstlinger F, Ghémard O, Levi F, Bismuth H (2004) Rescue surgery for unresectable colorectal liver metastases downstaged by chemotherapy: a model to predict long-term survival. Ann Surg 240(4):644–657PubMedGoogle Scholar
  2. 2.
    Tournigand C, Andre 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 (2004) FOLFIRI followed by FOLFOX6 or the reverse sequence in advanced colorectal cancer: a randomized GERCOR study. J Clin Oncol 22:229–23Google Scholar
  3. 3.
    Falcone A, Ricci S, Brunetti I, Pfanner E, Allegrini G, Barbara C, Crino L, Benedetti G, Evangelista W, Fanchini L, Cortesi E, Picone V, Vitello S, Chiara S, Granetto C, Porcile G, Fioretto L, Orlandini C, Andreuccetti M, Masi G (2007) Phase III trial of infusional fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) compared with infusional fluorouracil, leucovorin, and irinotecan (FOLFIRI) as firstline treatment for metastatic colorectal cancer: the Gruppo Oncologico Nord Ovest. J Clin Oncol 25:1670–1676PubMedCrossRefGoogle Scholar
  4. 4.
    Van Cutsem E, Nowacki M, Lang I, Cascinu S, Shchepotin I, Maurel J, Rougier P, Cunningham D, Nippgen J, Köhne C (2007) Randomized phase III study of irinotecan and 5-FU/FA with or without cetuximab in the first-line treatment of patients with metastatic colorectal cancer (mCRC): the CRYSTAL trial. J Clin Oncol 25(18S suppl):A4000Google Scholar
  5. 5.
    Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W, Berlin J, Baron A, Griffing S, Holmgren E, Ferrara N, Fyfe G, Rogers B, Ross R, Kabbinavar F (2004) Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 350:2335–2342PubMedCrossRefGoogle Scholar
  6. 6.
    Livermetsurvey (2011) Livermetsurvey, an international registry on colorectal liver metastases. At: www.livermetsurvey.org. Last accessed August 15, 2011
  7. 7.
    Cassidy J, Cunningham D, Berry SR, Rivera F, Clarke SJ, Kretzschmar A, Díaz-Rubio E, Van Cutsem E, Saltz LB (2008) Surgery with curative intent in patients (pts) treated with first-line chemotherapy (CT) + bevacizumab (BEV) for metastatic colorectal cancer (mCRC): first BEAT and NO16966. J Clin Oncol 26(15S suppl):A4022Google Scholar
  8. 8.
    Okines A, Puerto OD, Cunningham D et al (2009) Surgery with curative-intent in patients treated with first-line chemotherapy plus bevacizumab for metastatic colorectal cancer First BEAT and the randomized phase-III NO16966 trial. Br J Cancer 101(7):1033–1038PubMedCrossRefGoogle Scholar
  9. 9.
    Van Cutsem E, Köhne CH, Láng I, Folprecht G, Nowacki MP, Cascinu S, Shchepotin I, Maurel J, Cunningham D, Tejpar S, Schlichting M, Zubel A, Celik I, Rougier P, Ciardiello F (2011) 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 29(15):2011–2019PubMedCrossRefGoogle Scholar
  10. 10.
    Bokemeyer C, Bondarenko I, Hartmann JT, de Braud F, Schuch G, Zubel A, Celik I, Schlichting M, Koralewski P (2011) 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):1535–1546PubMedCrossRefGoogle Scholar
  11. 11.
    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, Błasińska-Morawiec M, Šmakal M, Canon JL, Rother M, Oliner KS, Wolf M, Gansert J (2010) 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(31):4697–4705PubMedCrossRefGoogle Scholar
  12. 12.
    Higgins JPT, Green S (editors) (2011) Cochrane handbook for systematic reviews of interventions version 5.1.0 [updated March 2011]. The Cochrane Collaboration. Available at: www.cochrane-handbook.org. Accessed 20 Aug 2011
  13. 13.
    DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7:177–188PubMedCrossRefGoogle Scholar
  14. 14.
    Kohne C, Bokemeyer C, Heeger S et al (2011) Efficacy of chemotherapy plus cetuximab according to metastatic site in KRAS wild-type metastatic colorectal cancer (mCRC): analysis of CRYSTAL and OPUS studies. J Clin Oncol 29: (suppl; abstr 3576)Google Scholar
  15. 15.
    Maughan TS, Adams RA, Smith CG et al (2011) 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. Lancet 377(9783):2103–2114PubMedCrossRefGoogle Scholar
  16. 16.
    Adam R, Wicherts DA, de Haas RJ et al (2009) Patients with initially unresectable colorectal liver metastases: is there a possibility of cure? J Clin Oncol 27(11):1829–1835PubMedCrossRefGoogle Scholar
  17. 17.
    Folprecht G, Grothey A, Alberts S, Raab HR, Köhne CH (2005) Neoadjuvant treatment of unresectable colorectal liver metastases: correlation between tumour response and resection rates. Ann Oncol 16(8):1311–1319PubMedCrossRefGoogle Scholar
  18. 18.
    Falcone A, Masi G, Loupakis F et al (2008) FOLFOXIRI (irinotecan, oxaliplatin, and infusional 5FU/LV) in combination with bevacizumab (BV) in the first-line treatment of metastatic colorectal cancer (mCRC): a phase II study by the G.O.N.O. group. J Clin Oncol 26:4031, AbstractGoogle Scholar

Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • F. Petrelli
    • 1
  • S. Barni
    • 1
  • Anti-EGFR agents for liver metastases
  1. 1.Medical Oncology Unit, Oncology departmentAzienda Ospedaliera Treviglio CaravaggioTreviglioItaly

Personalised recommendations