Epidermal growth factor receptor-targeted treatment strategies in advanced pancreatic cancer: Is K-RAS mutational testing ready for prime time?

The combination of gemcitabine with erlotinib is viewed as one standard in the treatment of patients with advanced pancreatic cancer. However, the magnitude of the survival benefit of the combination therapy compared to single agent gemcitabine is relatively small. Whether this statistically significant survival benefit translates to a relevant clinical benefit of the combined treatment in view of increased toxicity and costs is still a matter of debate. Consequently, there has been great interest in identifying molecular biomarkers predictive for response and survival benefit from EGFR-targeted agents in advanced pancreatic cancer. No data have been published up to now concerning the value of K-RAS mutations in pancreatic cancer as a predictive marker for lack of response to EGFR targeted agents. Nevertheless, the first prospective evaluation of K-RAS status and response to erlotinib in combination with either gemcitabine or capecitabine suggest a significant improvement of overall survival only for patients with K-RAS wild type tumors suggesting a possible role of K-RAS mutational status as predictive marker in pancreatic cancer. © Springer-Verlag 2011.