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Freeman DJ, Juan T, Reiner M, Hecht JR, Meropol NJ, Berlin J, Mitchell E, Sarosi I, Radinsky R, Amado RG
Association of k-ras mutational status and clinical outcomes in patients with metastatic colorectal. cancer receiving panitumumab alone
Clinical Colorectal Cancer (2008) 7:184-190.
Abstract
Background: Identifying predictive biomarkers is important to optimally treat patients. This analysis evaluated the association of K-ras,BRAF,and PIK3CA gene mutations with tumor resistance to panitumumab alone. Patients and Methods: From 3 phase 11 panitumumab metastatic colorectal cancer (mCRC) studies, 62 of 533 patient samples were available. Mutations were identified from genomic DNA by sequencing. Results: Of the 62 samples, 24 (38.7%) harbored a K-ras mutation, and 38 (61.3%) were wild type. In the wild-type K-ras group, 11% of patients had a partial response (PR), 53% had stable disease (SD), and 37% had progressive disease (PD). In the mutant K-ras group, 21% of patients had SD, and 79% of patients had PD; there were no responses. The absence of a K-ras mutation was associated with response to panitumumab (PR vs. SD vs. PD; P=.0028). The hazard ratio for wild-type versus mutant K-ras was 0.4 (95% Cl, 0.2-0.7) for progression-free survival and 0.5 (95% Cl, 0.3-0.9) for overall survival. Four patients had aV600E BRAF mutation, and 2 patients had a PIK3CA mutation. Conclusion: These data suggest that patients with mCRC with activating K-ras mutations are less likely to respond to panitumumab alone. The small sample size limits us from defining a predictive role of PIK3CA and BRAF mutations for panitumumab treatment.
Note
Publication Date: 2008-05-01.
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