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KRAS mutation status is not predictive for objective response to anti-EGFR treatment with erlotinib in patients with advanced pancreatic cancer

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Abstract

Background

It has not yet been defined if KRAS has a prognostic value or is a predictive biomarker for the efficacy of erlotinib in advanced pancreatic cancer (PC).

Methods

AIO-PK0104 was a phase III trial comparing gemcitabine/erlotinib followed by capecitabine with capecitabine/erlotinib followed by gemcitabine in advanced PC. For this post hoc subgroup analysis, biomarker data on the KRAS exon 2 mutation status were correlated with objective response to 1st-line therapy and with overall survival after start of 2nd-line chemotherapy (OSc).

Results

KRAS codon 12 was mutated in 121 of 173 (70 %) patients. The KRAS status showed no association with objective response (p = 0.40), but KRAS wildtype patients had an improved OS (HR 1.68, p = 0.005). A trend for a survival benefit was also observed during (non-erlotinib containing) 2nd-line chemotherapy, with a HR of 1.47 (p = 0.10) for the OSc.

Conclusion

This post hoc analysis of AIO-PK0104 supports the assumption that KRAS is rather a prognostic than a predictive biomarker in PC.

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References

  1. Heinemann V, Haas M, Boeck S. Systemic treatment of advanced pancreatic cancer. Cancer Treat Rev. 2012;38:843–53.

    Article  PubMed  CAS  Google Scholar 

  2. Lee J, Jang KT, Ki CS, Lim T, Park YS, Lim HY, et al. Impact of epidermal growth factor receptor (EGFR) kinase mutations, EGFR gene amplifications, and KRAS mutations on survival of pancreatic adenocarcinoma. Cancer. 2007;109:1561–9.

    Article  PubMed  CAS  Google Scholar 

  3. Chen H, Tu H, Meng ZQ, Chen Z, Wang P, Liu LM. K-ras mutational status predicts poor prognosis in unresectable pancreatic cancer. Eur J Surg Oncol. 2010;36:657–62.

    Article  PubMed  CAS  Google Scholar 

  4. Ogura T, Yamao K, Hara K, Mizuno N, Hijioka S, Imaoka H, et al. Prognostic value of K-ras mutation status and subtypes in endoscopic ultrasound-guided fine-needle aspiration specimens from patients with unresectable pancreatic cancer. J Gastroenterol. 2012; Sep 15 [Epub ahead of print].

  5. Kim ST, Lim do H, Jang KT, Lim T, Lee J, Choi YL, et al. Impact of KRAS mutations on clinical outcomes in pancreatic cancer patients treated with first-line gemcitabine-based chemotherapy. Mol Cancer Ther. 2011;10:1993–9.

    Article  PubMed  CAS  Google Scholar 

  6. Heinemann V, Vehling-Kaiser U, Waldschmidt D, Kettner E, Märten A, Winkelmann C, et al. Gemcitabine plus erlotinib followed by capecitabine versus capecitabine plus erlotinib followed by gemcitabine in advanced pancreatic cancer: final results of a randomised phase 3 trial of the ‘Arbeitsgemeinschaft Internistische Onkologie’ (AIO-PK0104). Gut. 2012; July 7 [Epub ahead of print].

  7. Boeck S, Jung A, Laubender RP, Neumann J, Egg R, Goritschan C, et al. EGFR pathway biomarkers in erlotinib-treated patients with advanced pancreatic cancer: translational results from the randomised, cross-over phase 3 trial AIO-PK0104. Br J Cancer. 2013;108(2):469–76.

    Google Scholar 

  8. Van Cutsem E, Köhne CH, Láng I, Folprecht G, Nowacki MP, Cascinu S, 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;29:2011–9.

    Article  PubMed  Google Scholar 

  9. Rosell R, Carcereny E, Gervais R, Vergnenegre A, Massuti B, Felip E, et al. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2012;13:239–46.

    Article  PubMed  CAS  Google Scholar 

  10. Da Cunha Santos G, Dhani N, Tu D, Chin K, Ludkovski O, Kamel-Reid S, et al. Molecular predictors of outcome in a phase 3 study of gemcitabine and erlotinib therapy in patients with advanced pancreatic cancer: National Cancer Institute of Canada Clinical Trials Group Study PA.3. Cancer. 2010;116:5599–607.

    Article  PubMed  Google Scholar 

  11. Modest DP, Brodowicz T, Stintzing S, Jung A, Neumann J, Laubender RP, et al. Impact of the specific mutation in KRAS codon 12 mutated tumors on treatment efficacy in patients with metastatic colorectal cancer receiving cetuximab-based first-line therapy: a pooled analysis of three trials. Oncology. 2012;83:241–7.

    Article  PubMed  CAS  Google Scholar 

  12. Amador ML, Oppenheimer D, Perea S, Maitra A, Cusatis G, Iacobuzio-Donahue C, et al. An epidermal growth factor receptor intron 1 polymorphism mediates response to epidermal growth factor receptor inhibitors. Cancer Res. 2004;64:9139–43.

    Article  PubMed  CAS  Google Scholar 

  13. Tzeng CW, Frolov A, Frolova N, Jhala NC, Howard JH, Vickers SM, et al. Pancreatic cancer epidermal growth factor receptor (EGFR) intron 1 polymorphism influences postoperative patient survival and in vitro erlotinib response. Ann Sur Oncol. 2007;14:2150–8.

    Article  Google Scholar 

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Acknowledgments

The authors wish to thank all patients and their families, nurses, study coordinators and investigators for their participation in the AIO-PK0104 study. Additionally, the active commitment of the pathologists providing FFPE archival tumor tissue is gratefully acknowledged because they enabled these important translational studies. Funded by Roche Pharma AG, Germany and Sturm-Stiftung, City of Munich, Germany.

Conflict of interest

Stefan Boeck received honoraria for scientific presentations, research funding, and travel grants from Roche. Dominik Modest also received a travel grant from Roche. Volker Heinemann serves as a consultant for Roche, and received honoraria for scientific presentations and research funding from Roche. All other authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Internal Medicine III and Comprehensive Cancer Center, Klinikum Grosshadern, Ludwig-Maximilians-University of Munich, Marchioninistr. 15, 81377, Munich, Germany

    Stefan Boeck, Rosalind Egg, Clara Goritschan, Michael Haas, Dominik P. Modest & Volker Heinemann

  2. Department of Pathology, Ludwig-Maximilians-University of Munich, Munich, Germany

    Andreas Jung, Jens Neumann, Rosalind Egg, Clara Goritschan, Steffen Ormanns & Thomas Kirchner

  3. Institute of Medical Informatics, Biometry and Epidemiology, Ludwig-Maximilians-University of Munich, Minich, Germany

    Rüdiger P. Laubender

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  1. Stefan Boeck
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  2. Andreas Jung
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Corresponding author

Correspondence to Stefan Boeck.

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Boeck, S., Jung, A., Laubender, R.P. et al. KRAS mutation status is not predictive for objective response to anti-EGFR treatment with erlotinib in patients with advanced pancreatic cancer. J Gastroenterol 48, 544–548 (2013). https://doi.org/10.1007/s00535-013-0767-4

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  • DOI: https://doi.org/10.1007/s00535-013-0767-4

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