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

• Published in: Journal of gastroenterology Vol. 48; no. 4; pp. 544 - 548
• Main Authors: Boeck, Stefan, Jung, Andreas, Laubender, Rüdiger P., Neumann, Jens, Egg, Rosalind, Goritschan, Clara, Ormanns, Steffen, Haas, Michael, Modest, Dominik P., Kirchner, Thomas, Heinemann, Volker
• Format: Journal Article
• Language: English
• Published: Japan Springer Japan 01.04.2013; Springer; Springer Nature B.V
• Subjects: Abdominal Surgery; Adult; Aged; Analysis; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biomarkers, Tumor - genetics; Cancer; Cancer patients; Care and treatment; Chemotherapy; Codon; Colorectal Surgery; Cross-Over Studies; Erlotinib; Erlotinib Hydrochloride; Female; Gastroenterology; Genetic aspects; Hepatology; Humans; Kaplan-Meier Estimate; KRAS; Male; Medicine; Medicine & Public Health; Middle Aged; Mutation; Neoplasm Proteins - metabolism; Pancreatic cancer; Pancreatic Neoplasms - drug therapy; Pancreatic Neoplasms - genetics; Pancreatic Neoplasms - metabolism; Prognosis; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins p21(ras); Quinazolines - administration & dosage; Rapid Communication; ras Proteins - genetics; Receptor, Epidermal Growth Factor - antagonists & inhibitors; Receptor, Epidermal Growth Factor - genetics; Receptor, Epidermal Growth Factor - metabolism; Surgical Oncology; Treatment Outcome; Erlotinib; Pancreatic cancer; KRAS
• ISSN: 0944-1174; 1435-5922; 1435-5922
• DOI: 10.1007/s00535-013-0767-4

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.