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 II 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% CI, 0.2-0.7) for progression-free survival and 0.5 (95% CI, 0.3-0.9) for overall survival. Four patients had a V600E 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.
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 II 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% CI, 0.2-0.7) for progression-free survival and 0.5 (95% CI, 0.3-0.9) for overall survival. Four patients had a V600EBRAF 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.
Authors: Efsevia Vakiani; Manickam Janakiraman; Ronglai Shen; Rileen Sinha; Zhaoshi Zeng; Jinru Shia; Andrea Cercek; Nancy Kemeny; Michael D'Angelica; Agnes Viale; Adriana Heguy; Philip Paty; Timothy A Chan; Leonard B Saltz; Martin Weiser; David B Solit Journal: J Clin Oncol Date: 2012-06-04 Impact factor: 44.544
Authors: Sandra Van Schaeybroeck; Wendy L Allen; Richard C Turkington; Patrick G Johnston Journal: Nat Rev Clin Oncol Date: 2011-02-15 Impact factor: 66.675
Authors: Elizabeth A Hopper-Borge; Rochelle E Nasto; Vladimir Ratushny; Louis M Weiner; Erica A Golemis; Igor Astsaturov Journal: Expert Opin Ther Targets Date: 2009-03 Impact factor: 6.902