Skip to main content

Advertisement

SpringerLink
Log in

Cetuximab-based Therapy is Effective in Chemotherapy-naïve Patients with Advanced and Metastatic Non-small-cell Lung Cancer: A Meta-analysis of Randomized Controlled Trials

  • Published:
Lung Aims and scope Submit manuscript

Abstract

Randomized controlled trails (RCTs) where cetuximab added to first-line platinum-based chemotherapy for patients with advanced/metastatic non-small-cell lung cancer (NSCLC) have yielded conflicting results. This meta-analysis intended to evaluate the efficacy and safety of cetuximab-based therapy (CBT) in that setting. We analyzed four eligible RCTs that included 1,003 and 1,015 patients randomized to CBT and control intervention, respectively. As compared with the noncetuximab group, CBT demonstrated an 9% reduction in the risk of disease progression [hazard ratio (HR) = 0.91; (CI = 0.83–1.00); p = 0.06], a 13% reduction in the risk of death [HR = 0.87; (CI = 0.78–0.96); p = 0.005], and an approximately 50% increase in objective response rate [odds ratio (OR) = 1.48; (CI = 1.22–1.80); p < 0.0001]. CBT-related adverse events were similar across comparisons except for toxicities known to be associated with anti-EGFR therapy. CBT produced significant clinical benefit with acceptable toxicity as a first-line strategy in patients with advanced/metastatic NSCLC. Further research is needed to identify markers predictive of cetuximab benefit in that disease.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM (2010) Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 127(12):2893–2917

    Article  PubMed  CAS  Google Scholar 

  2. Jemal A, Siegel R, Xu J, Ward E (2010) Cancer statistics, 2010. CA Cancer J Clin 60:277–300

    Article  PubMed  Google Scholar 

  3. Stinchcombe TE, Bogart J, Wigle DA, Govindan R (2010) Annual review of advances in lung cancer clinical research: a report for the year 2009. J Thorac Oncol 5:935–939

    Article  PubMed  Google Scholar 

  4. Herbst RS, Shin DM (2002) Monoclonal antibodies to target epidermal growth factor receptor-positive tumors: a new paradigm for cancer therapy. Cancer 94:1593–1611

    Article  PubMed  CAS  Google Scholar 

  5. Rusch V, Klimstra D, Venkatraman E, Pisters PW, Langenfeld J, Dmitrovsky E (1997) Overexpression of the epidermal growth factor receptor and its ligand transforming growth factor alpha is frequent in resectable non-small cell lung cancer but does not predict tumor progression. Clin Cancer Res 3:515–522

    PubMed  CAS  Google Scholar 

  6. Brabender J, Danenberg KD, Metzger R, Schneider PM, Park J, Salonga D, Holscher AH, Danenberg PV (2001) Epidermal growth factor receptor and HER2-neu mRNA expression in non-small cell lung cancer Is correlated with survival. Clin Cancer Res 7:1850–1855

    PubMed  CAS  Google Scholar 

  7. Kurai J, Chikumi H, Hashimoto K, Yamaguchi K, Yamasaki A, Sako T, Touge H, Makino H, Takata M, Miyata M, Nakamoto M, Burioka N, Shimizu E (2007) Antibody-dependent cellular cytotoxicity mediated by cetuximab against lung cancer cell lines. Clin Cancer Res 13:1552–1561

    Article  PubMed  CAS  Google Scholar 

  8. Mendelsohn J, Baselga J (2003) Status of epidermal growth factor receptor antagonists in the biology and treatment of cancer. J Clin Oncol 21:2787–2799

    Article  PubMed  CAS  Google Scholar 

  9. Pirker R, Pereira JR, Szczesna A, von Pawel J, Krzakowski M, Ramlau R, Vynnychenko I, Park K, Yu CT, Ganul V, Roh JK, Bajetta E, O’Byrne K, de Marinis F, Eberhardt W, Goddemeier T, Emig M, Gatzemeier U (2009) Cetuximab plus chemotherapy in patients with advanced non-small-cell lung cancer (FLEX): an open-label randomised phase III trial. Lancet 373:1525–1531

    Article  PubMed  CAS  Google Scholar 

  10. Lynch TJ, Patel T, Dreisbach L, McCleod M, Heim WJ, Hermann RC, Paschold E, Iannotti NO, Dakhil S, Gorton S, Pautret V, Weber MR, Woytowitz D (2010) Cetuximab and first-line taxane/carboplatin chemotherapy in advanced non-small-cell lung cancer: results of the randomized multicenter phase III trial BMS099. J Clin Oncol 28:911–917

    Article  PubMed  CAS  Google Scholar 

  11. Parmar MK, Torri V, Stewart L (1998) Extracting summary statistics to perform meta-analyses of the published literature for survival endpoints. Stat Med 17:2815–2834

    Article  PubMed  CAS  Google Scholar 

  12. Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315:629–634

    PubMed  CAS  Google Scholar 

  13. Lau J, Ioannidis JP, Schmid CH (1997) Quantitative synthesis in systematic reviews. Ann Intern Med 127:820–826

    PubMed  CAS  Google Scholar 

  14. Shakespeare TP, Gebski VJ, Veness MJ, Simes J (2001) Improving interpretation of clinical studies by use of confidence levels, clinical significance curves, and risk-benefit contours. Lancet 357:1349–1353

    Article  PubMed  CAS  Google Scholar 

  15. Liu L, Cao Y, Tan A, Liao C, Gao F (2010) Cetuximab-based therapy versus non-cetuximab therapy for advanced cancer: a meta-analysis of 17 randomized controlled trials. Cancer Chemother Pharmacol 65:849–861

    Article  PubMed  CAS  Google Scholar 

  16. Butts CA, Bodkin D, Middleman EL, Englund CW, Ellison D, Alam Y, Kreisman H, Graze P, Maher J, Ross HJ, Ellis PM, McNulty W, Kaplan E, Pautret V, Weber MR, Shepherd FA (2007) Randomized phase II study of gemcitabine plus cisplatin or carboplatin [corrected], with or without cetuximab, as first-line therapy for patients with advanced or metastatic non small-cell lung cancer. J Clin Oncol 25:5777–5784

    Article  PubMed  CAS  Google Scholar 

  17. Rosell R, Robinet G, Szczesna A, Ramlau R, Constenla M, Mennecier BC, Pfeifer W, O’Byrne KJ, Welte T, Kolb R, Pirker R, Chemaissani A, Perol M, Ranson MR, Ellis PA, Pilz K, Reck M (2008) Randomized phase II study of cetuximab plus cisplatin/vinorelbine compared with cisplatin/vinorelbine alone as first-line therapy in EGFR-expressing advanced non-small-cell lung cancer. Ann Oncol 19:362–369

    Article  PubMed  CAS  Google Scholar 

  18. Ibrahim EM (2010) Frontline gefitinib in advanced non-small cell lung cancer: meta-analysis of published randomized trials. Ann Thorac Med 5:153–160

    Article  PubMed  Google Scholar 

  19. Herbst RS, Prager D, Hermann R, Fehrenbacher L, Johnson BE, Sandler A, Kris MG, Tran HT, Klein P, Li X, Ramies D, Johnson DH, Miller VA (2005) TRIBUTE: a phase III trial of erlotinib hydrochloride (OSI-774) combined with carboplatin and paclitaxel chemotherapy in advanced non-small-cell lung cancer. J Clin Oncol 23:5892–5899

    Article  PubMed  CAS  Google Scholar 

  20. Gatzemeier U, Pluzanska A, Szczesna A, Kaukel E, Roubec J, De Rosa F, Milanowski J, Karnicka-Mlodkowski H, Pesek M, Serwatowski P, Ramlau R, Janaskova T, Vansteenkiste J, Strausz J, Manikhas GM, Von Pawel J (2007) Phase III study of erlotinib in combination with cisplatin and gemcitabine in advanced non-small-cell lung cancer: the Tarceva Lung Cancer Investigation Trial. J Clin Oncol 25:1545–1552

    Article  PubMed  CAS  Google Scholar 

  21. Paez JG, Janne PA, Lee JC, Tracy S, Greulich H, Gabriel S, Herman P, Kaye FJ, Lindeman N, Boggon TJ, Naoki K, Sasaki H, Fujii Y, Eck MJ, Sellers WR, Johnson BE, Meyerson M (2004) EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 304:1497–1500

    Article  PubMed  CAS  Google Scholar 

  22. Tsao MS, Sakurada A, Cutz JC, Zhu CQ, Kamel-Reid S, Squire J, Lorimer I, Zhang T, Liu N, Daneshmand M, Marrano P, da Cunha Santos G, Lagarde A, Richardson F, Seymour L, Whitehead M, Ding K, Pater J, Shepherd FA (2005) Erlotinib in lung cancer—molecular and clinical predictors of outcome. N Engl J Med 353:133–144

    Article  PubMed  CAS  Google Scholar 

  23. Khambata-Ford S, Harbison CT, Hart LL, Awad M, Xu LA, Horak CE, Dakhil S, Hermann RC, Lynch TJ, Weber MR (2010) Analysis of potential predictive markers of cetuximab benefit in BMS099, a phase III study of cetuximab and first-line taxane/carboplatin in advanced non-small-cell lung cancer. J Clin Oncol 28:918–927

    Article  PubMed  CAS  Google Scholar 

  24. Herbst RS, Kelly K, Chansky K, Mack PC, Franklin WA, Hirsch FR, Atkins JN, Dakhil SR, Albain KS, Kim ES, Redman M, Crowley JJ, Gandara DR (2010) Phase II selection design trial of concurrent chemotherapy and cetuximab versus chemotherapy followed by cetuximab in advanced-stage non-small-cell lung cancer: Southwest Oncology Group study S0342. J Clin Oncol 28:4747–4754

    Article  PubMed  CAS  Google Scholar 

  25. Crawford J, Swanson P, Prager D, Schwarzenberger P, Sandier A, Schiller J, Johnson D, Navale L, Moss S, Jerian S (2005) Panitumumab, a fully human antibody, combined with paclitaxel and carboplatin versus paclitaxel and carboplatin alone for first line advanced non-small cell lung cancer (NSCLC): a primary analysis. Eur J Cancer 3:324

    Google Scholar 

  26. Fleming TR, Rothmann MD, Lu HL (2009) Issues in using progression-free survival when evaluating oncology products. J Clin Oncol 27:2874–2880

    Article  PubMed  Google Scholar 

  27. Buyse M, Burzykowski T, Carroll K, Michiels S, Sargent DJ, Miller LL, Elfring GL, Pignon JP, Piedbois P (2007) Progression-free survival is a surrogate for survival in advanced colorectal cancer. J Clin Oncol 25:5218–5224

    Article  PubMed  CAS  Google Scholar 

  28. Gridelli C, Mencoboni M, Carrozza F, Vigano MG, Gebbia V, Verusio C, Maione P, Gallo C, Perrone F, Ciardiello F (2008) Cetuximab (C) and gemcitabine (G) in elderly or adult PS2 advanced non small-cell lung cancer (NSCLC) patients (pts): the CALC1 randomised phase II trials. ASCO Meeting Abstracts 26:8117

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Oncology Center of Excellence, International Medical Center, PO Box 2172, Jeddah, 21451, Kingdom of Saudi Arabia

    Ezzeldin M. Ibrahim, Khaled M. Abouelkhair, Osama A. Al-Masri, Najeeb C. Chaudry & Ghieth A. Kazkaz

Authors
  1. Ezzeldin M. Ibrahim
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Khaled M. Abouelkhair
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Osama A. Al-Masri
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Najeeb C. Chaudry
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ghieth A. Kazkaz
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ezzeldin M. Ibrahim.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ibrahim, E.M., Abouelkhair, K.M., Al-Masri, O.A. et al. Cetuximab-based Therapy is Effective in Chemotherapy-naïve Patients with Advanced and Metastatic Non-small-cell Lung Cancer: A Meta-analysis of Randomized Controlled Trials. Lung 189, 193–198 (2011). https://doi.org/10.1007/s00408-011-9286-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00408-011-9286-3

Keywords

Search

Navigation