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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

Journal of Gastroenterology volume 48, pages 544–548 (2013)Cite this article

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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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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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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  3. Rüdiger P. Laubender
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  4. Jens Neumann
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  5. Rosalind Egg
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  6. Clara Goritschan
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  7. Steffen Ormanns
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  8. Michael Haas
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  9. Dominik P. Modest
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  10. Thomas Kirchner
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  11. Volker Heinemann
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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

Keywords

  • Erlotinib
  • KRAS
  • Pancreatic cancer