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

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.

• Authors: Stefan Boeck, Andreas Jung, Rüdiger P Laubender, Jens Neumann, Rosalind Egg, Clara Goritschan, Steffen Ormanns, Michael Haas, Dominik P Modest, Thomas Kirchner, Volker Heinemann
• Journal: Journal of gastroenterology (J Gastroenterol) Vol. 48 Issue 4 Pg. 544-8 (Apr 2013) ISSN: 1435-5922 [Electronic] Japan
• PMID: 23435671 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• KRAS protein, human
• Neoplasm Proteins
• Proto-Oncogene Proteins
• Quinazolines
• Erlotinib Hydrochloride
• ErbB Receptors
• Proto-Oncogene Proteins p21(ras)
• ras Proteins

Topics

• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Biomarkers, Tumor (genetics)
• Cross-Over Studies
• ErbB Receptors (antagonists & inhibitors, genetics, metabolism)
• Erlotinib Hydrochloride
• Female
• Humans
• Kaplan-Meier Estimate
• Male
• Middle Aged
• Mutation
• Neoplasm Proteins (metabolism)
• Pancreatic Neoplasms (drug therapy, genetics, metabolism)
• Prognosis
• Proto-Oncogene Proteins (genetics)
• Proto-Oncogene Proteins p21(ras)
• Quinazolines (administration & dosage)
• Treatment Outcome
• ras Proteins (genetics)