Analysis Of Efficacy And Prognostic Factors Of Cetuximab In The Treatment Of Metastatic Colorectal Cancer

Objective:The aim of our study is to explore the prognostic and predictive clinical pathological characteristics and biomarkers for cetuximab therapy in metastatic colorectal cancer(mCRC)with KRAS/ALL-RAS wide-type(WT).Methods:mCRC patients treated with cetuximab from November 2007 to December 2016 in the department of medical oncology in Peking Union Medical College Hospital were enrolled for analysis.All patients were pathologically diagnosed adenocarcinoma with KRAS-WT(ARMS)or All-RAS-WT(next generation sequencing).We analysed the relationship between the efficacy and clinical pathological characteristics,as well as the expression level of EGFR,HER2,c-MET and PTEN through immunohistochemistry,along with gene mutations via the next-generation sequencing.Results:1.Sixty patients treated with cetuximab were enrolled.For the 34 patients receiving cetuximab as first-line treatment,the objective response rate(ORR)was 55.9%,and the progression free survival(PFS)and overall survival(OS)was 11 and 24 months,respectively.The ORR was 15.0%,PFS was 10 months,and OS was 29 months among the 20 patients receiving cetuximab as second-line treatment.The ORR was 22.2%,PFS was 8 months,and OS was 22 months among the 18 patients receiving cetuximab as third-line treatment.2.Patients continuously treated with cetuximab beyond first-line progression had longer median OS than those discontinuing cetuximab among the 34 patients receiving cetuximab therapy as first-line treatment.(HR=0.251,95%CI:0.066?0.948,p=0.041).3.Patients with left-sided colon cancer had higher ORR(62.1%vs 0.0%,p=0.033)and longer PFS(11 months vs 4 months,p=0.068)than those with right-sided colon cancer among the 34 patients receiving cetuximab therapy as first-line treatment.4.Patients with All-RAS-WT had lower risk of progrssion than those just known KRAS-WT when receiving cetuximab as first-line or third-line and above treatment(first-line:HR=0.313,p=0.022;third-line and above:HR=0.242,p=0.026).When compared with the 24 All-RAS-WT mCRC patients treated with chemotherapy alone,All-RAS-WT patients receiving chemotherapy combined with cetuximab as first-line treatment had higher ORR(52.9%vs 25%,p=0.067).5.Among 27 KRAS/A LL-RA S wide-type mCRC patients with results of immunohistochemistry,3 cases with high expression of c-MET had poor efficacy(1 PD,2 SD),ORR was lower in patients with loss of PTEN expression than in those with normal expression(26.7%vs 75.0%),and 3 cases with increased HER2 gene copy number(GCN)had poor efficacy(1 PD,2 SD).6.Among 29 All-RAS-WT mCRC patients,all the 3 cases with PIK3CA gene mutation,3 cases with PTEN gene mutation,and 2 cases with SMAD4 gene mutation had poor efficacy(the responses were 3SD,1PD and 2SD,2SD,respectively).One case with CDKN2A gene mutation and another case with FBXW7 gene mutation had also poor efficacy(both were SD).Conclusion:Continuing cetuximab treatment beyond progression may reduce the risk of death among KRAS/ALL-RAS WT mCRC patients benefitting from first-line cetuximab treatment.The efficacy of left-sided colon cancer was better than that of right-sided colon cancer among KRAS/ALL-RAS WT mCRC patients receiving cetuximab.Patients with All-RAS-WT had lower risk of progression than those with KRAS-WT.Besides RAS,the expression and mutation of other biomarkers such as PTEN?c-MET?PIK3CA?HER2 might be associated with the efficacy of cetuximab in KRAS-WT mCRC patients.