Activating KRAS Mutations and Overexpression of Epidermal Growth Factor Receptor as Independent Predictors in Metastatic Colorectal Cancer Patients Treated With Cetuximab

摘要: Objective: Cetuximab, a monoclonal antibody targeting epidermal growth factor receptor (EGFR), has been proven to be efficient in metastatic colorectal cancer (mCRC); however, the therapeutic response is variable and markers predictive of are urgently required. This study was conducted determinate values KRAS mutation status EGFR expression mCRC patients treated with cetuximab plus chemotherapy. Summary Background Data: Clinical benefit EGFR-targeting antibodies seems restricted particular subgroup patients. Therefore, identification reliable factors for imperative before introduction targeted Methods: Ninety-five receiving FOLFIRI or FOLFOX-4 chemotherapy were enrolled into present study. status/EGFR levels analyzed using direct sequencing, immunohistochemistry (IHC), reverse transcription-polymerase chain reaction (RT-PCR) assay, respectively. The association between clinical response, progression-free survival (PFS) overall (OS) as well evaluated. Results: Of 95 patients, mutations identified 41 cases, overexpression (protein mRNA levels) observed 78 Among tumors mutation, 33 found activating mutants at codons 12, 13, 15 18, while 8 nonactivating 20, 30, 31. Fifty-five responded chemotherapy, 49 46 wild-type tumor status. Patients that express high harbor more likely have better PFS OS when (all P 0.05). Furthermore, had significantly than (both However, status, remains relevant predictor response. Conclusions: suggests particularly important independent marker which combing could help identify who most respond