***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: In a r and omised phase 3 trial , panitumumab significantly improved progression-free survival ( PFS ) in patients with refractory metastatic colorectal cancer ( mCRC ) . This analysis characterises the association of PFS with CRC symptoms , health-related quality of life ( HRQoL ) , and overall survival ( OS ) . CRC symptoms ( NCCN/FACT CRC symptom index , FCSI ) and  HRQoL  ( EQ-5D ) were assessed for 207 panitumumab patients and 184 best supportive care ( BSC ) patients who had at least one post-baseline patient-reported outcome ( PRO ) assessment . Patients alive at week 8 were included in the PRO and OS analyses and categorised by their week 8 progression status as follows : no progressive disease ( no PD ; best response of at least stable disease ) vs progressive disease ( PD ) . St and ard imputation methods were used to assign missing values . Significantly more patients were progression free at weeks 8–24 with panitumumab vs BSC . After excluding responders , a significant difference in PFS remained favouring panitumumab ( HR=0.63 , 95 % CI=0.52–0.77 ; P<0.0001 ) . At week 8 , lack of disease progression was associated with significantly and clinical ly meaningful lower CRC symptomatology for both treatment groups and higher HRQoL  for panitumumab patients only . Overall survival favoured no PD patients vs PD patients alive at week 8 . Lack of disease progression was associated with better symptom control , HRQoL , and OS BACKGROUND Treatment with cetuximab , a monoclonal antibody directed against the epidermal growth factor receptor , improves overall and progression-free survival and preserves the quality of life in patients with colorectal cancer that has not responded to chemotherapy . The mutation status of the K-ras gene in the tumor may affect the response to cetuximab and have treatment-independent prognostic value . METHODS We analyzed tumor sample s , obtained from 394 of 572 patients ( 68.9 % ) with colorectal cancer who were r and omly assigned to receive cetuximab plus best supportive care or best supportive care alone  , to look for activating mutations in exon 2 of the K-ras gene . We assessed whether the mutation status of the K-ras gene was associated with survival in the cetuximab and supportive-care groups . RESULTS Of the tumors evaluated for K-ras mutations , 42.3 % had at least one mutation in exon 2 of the gene . The effectiveness of cetuximab was significantly associated with K-ras mutation status ( P=0.01 and P<0.001 for the interaction of K-ras mutation status with overall survival and progression-free survival , respectively ) . In patients with wild-type K-ras tumors , treatment with cetuximab as compared with supportive care alone significantly improved overall survival ( median , 9.5 vs. 4.8 months ; hazard ratio for death , 0.55 ; 95 % confidence interval [ CI ] , 0.41 to 0.74 ; P<0.001 ) and progression-free survival ( median , 3.7 months vs. 1.9 months ; hazard ratio for progression or death , 0.40 ; 95 % CI , 0.30 to 0.54 ; P<0.001 ) . Among patients with mutated K-ras tumors , there was no significant difference between those who were treated with cetuximab and those who received supportive care alone with respect to overall survival ( hazard ratio , 0.98 ; P=0.89 ) or progression-free survival ( hazard ratio , 0.99 ; P=0.96 ) . In the group of patients receiving best supportive care alone , the mutation status of the K-ras gene was not significantly associated with overall survival ( hazard ratio for death , 1.01 ; P=0.97 ) . CONCLUSIONS Patients with a colorectal tumor bearing mutated K-ras did not benefit from cetuximab , whereas patients with a tumor bearing wild-type K-ras did benefit from cetuximab . The mutation status of the K-ras gene had no influence on survival among patients treated with best supportive care alone . ( Clinical Trials.gov number , NCT00079066 . BACKGROUND Cetuximab , an IgG1 chimeric monoclonal antibody against epidermal growth factor receptor ( EGFR ) , has activity against colorectal cancers that express EGFR . METHODS From December 2003 to August 2005 , 572 patients who had colorectal cancer expressing immunohistochemically detectable EGFR and who had been previously treated with a fluoropyrimidine , irinotecan , and oxaliplatin or had contraindications to treatment with these drugs underwent r and omization to an initial dose of 400 mg of cetuximab per square meter of body-surface area followed by a weekly infusion of 250 mg per square meter plus best supportive care  ( 287 patients ) or best supportive care alone  ( 285 patients ) . The primary end point was overall survival . RESULTS In comparison with best supportive care alone , cetuximab treatment was associated with a significant improvement in overall survival ( hazard ratio for death , 0.77 ; 95 % confidence interval [ CI ] , 0.64 to 0.92 ; P=0.005 ) and in progression-free survival ( hazard ratio for disease progression or death , 0.68 ; 95 % CI , 0.57 to 0.80 ; P<0.001 ) . These benefits were robust after adjustment in a multivariable Cox proportional-hazards model . The median overall survival was 6.1 months in the cetuximab group and 4.6 months in the group assigned to supportive care alone . Partial responses occurred in 23 patients ( 8.0 % ) in the cetuximab group but in none in the group assigned to supportive care alone ( P<0.001 ) ; the disease was stable in an additional 31.4 % of patients assigned to cetuximab and in 10.9 % of patients assigned to supportive care alone ( P<0.001 ) . Quality of life was better preserved in the cetuximab group , with less deterioration in physical function and global health status scores ( both P<0.05 ) . Cetuximab treatment was associated with a characteristic rash ; a rash of grade 2 or higher was strongly associated with improved survival ( hazard ratio for death , 0.33 ; 95 % CI , 0.22 to 0.50 ; P<0.001 ) . The incidence of any adverse event of grade 3 or higher was 78.5 % in the cetuximab group and 59.1 % in the group assigned to supportive care alone ( P<0.001 ) . CONCLUSIONS Cetuximab improves overall survival and progression-free survival and preserves quality -of-life measures in patients with colorectal cancer in whom other treatments have failed . ( Clinical Trials.gov number , NCT00079066 [ Clinical Trials.gov ] . ) 
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SUMMARY OF FINDINGS OF SYSTEMATIC REVIEW : CETUXIMAB OR PANITUMUMAB MONOTHERAPY : Based on moderate GRADE observational evidence , there is improvement in PFS and OS favouring patients without the KRAS mutation ( KRAS wildtype , or KRAS WT ) compared to those with the mutation .
CETUXIMAB-IRINOTECAN COMBINATION THERAPY : There is low GRADE evidence that testing for KRAS may optimize survival benefits in patients without the KRAS mutation ( KRAS wildtype , or KRAS WT ) compared to those with the mutation .
However , cetuximab-irinotecan combination treatments based on KRAS status discount any effect of cetuximab in possibly reversing resistance to irinotecan in patients with the mutation , as observed effects were lower than for patients without the mutation .
KRAS status is predictive of outcomes in cetuximab and panitumumab monotherapy , and in cetuximab-irinotecan combination therapy .
While KRAS testing is cost-effective for all strategies considered , it is not equally cost-effective for all treatment options