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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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