Multiple studies have demonstrated an association between KRAS mutational status in the primary tumor and resistance to EGFR inhibitors (cetuximab and panitumumab) in patients with mCRC (18),(19). Recently based on convincing data, National Comprehensive Cancer Network (NCCN) has also made recommendation that patients with known KRAS mutations should not be treated with EGFR inhibitors (20). #C59 chemical structure randurls[1|1|,|CHEM1|]# Although there is robust data regarding the association of WT KRAS status and response to EGFR inhibitors, the relationship between KRAS MT and response Inhibitors,research,lifescience,medical to first line oxaliplatin based chemotherapy without anti-EGFR antibodies is conflicting. Two previous
first-line studies showed an improved trend in response rate (RR) and progression free survival (PFS) in mCRC patients with KRAS MT, who were treated with first line chemotherapy regimen including oxaliplatin without cetuximab or panitumumab while others have reported a worsened outlook for patients with KRAS MT who were treated similarly (Table 1) (21),(22). Inhibitors,research,lifescience,medical Table 1 Efficacy data of selected prospective studies in patients with known KRAS status In this study, we aimed to address
the impact of KRAS on the pattern of metastatic disease at presentation and on clinical outcome with first line FOLFOX chemotherapy. Patients and methods Study endpoints The Inhibitors,research,lifescience,medical primary endpoint of this study was to compare the progression free survival of KRAS WT and KRAS MT CRC patients treated with first-line FOLFOX (with or without bevacizumab) chemotherapy. Secondary endpoints included overall survival, response rate, and pattern of metastatic disease in the KRAS WT
and MT populations. Patient population All patients with metastatic Inhibitors,research,lifescience,medical colorectal cancer with a known KRAS status and who were treated at Roswell Park Cancer Institute (RPCI) with first-line FOLFOX or FOLFOX plus bevacizumab were eligible for this study (Fig 2). Most of these patients were treated at our institute. Patients who received first line chemotherapy at a community hospital were included in the study only if their imaging studies were available for response evaluation. Figure 2 Study scheme for assessment of outcome Inhibitors,research,lifescience,medical based on KRAS status in patients treated with first-line FOLFOX with or without Bevacizumab. CRC= colorectal cancer, mCRC= metastatic colorectal cancer, FOLFOX= Folinic acid, Fluorouracil, Oxaliplatin. Treatment plan First line chemotherapy consisted of oxaliplatin 85mg/m2 infused Electron transport chain over 2 hours; bevacizumab 5mg/kg intravenous (I.V) over 10 minutes; leucovorin (LV) 400mg/m2 infused during 2 hours, followed by fluorouracil (FU) as a 400mg/m2 I.V. bolus on day 1 then a 2.4 grams/m2 continuous infusion over 46 hours on a 14-day treatment cycle. Patients receiving bevacizumab were dosed at 5mg/Kg every 2 weeks on day 1 of FOLFOX. Efficacy assessment CT images for all the patients were reviewed by the investigators for evaluation of response. Response was assessed according to revised RECIST (version 1.