1. Impact of genetic profiles on the efficacy of anti-EGFR antibodies in metastatic colorectal cancer with KRAS mutation.
- Author
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Kishiki T, Ohnishi H, Masaki T, Ohtsuka K, Ohkura Y, Furuse J, Sugiyama M, and Watanabe T
- Subjects
- Adult, Aged, Aged, 80 and over, Antibodies, Monoclonal adverse effects, Antibodies, Monoclonal therapeutic use, Antibodies, Monoclonal, Humanized administration & dosage, Antibodies, Monoclonal, Humanized therapeutic use, Antineoplastic Agents therapeutic use, Camptothecin administration & dosage, Camptothecin analogs & derivatives, Camptothecin therapeutic use, Cetuximab, Colorectal Neoplasms genetics, Colorectal Neoplasms pathology, Drug Administration Schedule, Female, Humans, Irinotecan, Male, Middle Aged, Mutation, Neoplasm Metastasis genetics, Neoplasm Metastasis pathology, PTEN Phosphohydrolase genetics, Panitumumab, Proto-Oncogene Proteins c-met genetics, Proto-Oncogene Proteins p21(ras), Retrospective Studies, Treatment Outcome, Antibodies, Monoclonal administration & dosage, Antineoplastic Agents administration & dosage, Colorectal Neoplasms drug therapy, Gene Expression Regulation, Neoplastic drug effects, Neoplasm Metastasis drug therapy, Proto-Oncogene Proteins genetics, ras Proteins genetics
- Abstract
Reports indicate that, even in KRAS-mutated colon cancer, there are subsets of patients who benefit from anti-EGFR monoclonal antibody (MoAb) treatment. The aim of the present study was to identify genetic profiles that contribute to the responsiveness of metastatic colorectal cancer (mCRC) to anti-EGFR MoAb. We retrospectively evaluated the efficacy of anti-EGFR MoAb in mCRC patients with KRAS mutations according to KRAS mutational subtypes, BRAF and PIK3CA mutational status and PTEN and MET expression. Among 21 patients with KRAS-mutant tumors, 8 (38%) harbored p.G13D, 7 (33%) harbored p.G12V, 5 (24%) harbored p.G12D, and 1 (5%) harbored p.G12C mutation. Patients with the p.G13D mutation exhibited a significantly higher disease control rate than patients with other KRAS mutations (P=0.042), and tended to show a longer progression-free survival (PFS) than patients with other KRAS mutations with marginal significance (P=0.074). Patients with loss of PTEN had significantly shorter PFS than those with normal PTEN expression in patients with KRAS mutations (P=0.044). MET overexpression was significantly associated with shorter PFS compared to normal MET expression in patients with KRAS mutations (P=0.016). Our data demonstrated the potential utility of alterations in PTEN and MET expression as predictive markers for response to anti-EGFR MoAbs in mCRC patients with KRAS mutations. In addition, we confirmed the predictive value of the KRAS p.G13D mutation for better response to anti-EGFR therapies in comparison with other KRAS mutations.
- Published
- 2014
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