Chen J.S.CHIH-HUNG HSUChiang N.J.Tsai C.S.Tsou H.H.Huang S.F.Bai L.Y.Chang I.C.Shiah H.S.Ho C.L.Yen C.J.Lee K.D.Chiu C.F.Rau K.M.Yu M.S.Yang Y.Hsieh R.K.Chang J.Y.Shan Y.S.Chao Y.Chen L.-T.Chin Y.-H.Chung T.-R.Yu W.-L.Lee M.-H.Lin L.-F.Lin P.-C.Wu Y.-L.Wang H.-L.Lu L.-J.Chen S.-Y.Wu C.-C.Wei T.-C.on behalf of the Taiwan Cooperative Oncology Group2020-04-282020-04-2820150923-7534https://www.scopus.com/inward/record.uri?eid=2-s2.0-84929091392&doi=10.1093%2fannonc%2fmdv035&partnerID=40&md5=f0bb44f83285a369a70313438b0291d0https://scholars.lib.ntu.edu.tw/handle/123456789/487287Background: Previous clinical trials have not proved that adding epidermal growth factor receptor inhibitors to chemotherapy confers a survival benefit for patients with advanced biliary tract cancer (ABTC). Whether the KRAS mutation status of tumor cells confounded the results of past studies is unknown. Patients and methods: ABTC patients stratified by KRAS status, Eastern Cooperative Oncology Group performance status, and primary tumor location were randomized 1: 1 to receive GEMOX (800 mg/m2 gemcitabine and 85 mg/m2 oxaliplatin) or C-GEMOX (500 mg/m2 cetuximab plus GEMOX) every 2 weeks. The primary end point was objective response rate (ORR). Results: The study enrolled 122 patients between December 2010 and May 2012 (62 treated with C-GEMOX and 60 with GEMOX). Compared with GEMOX alone, C-GEMOX was associated with trend to better ORR (27% versus 15%; P=0.12) and progression-free survival (PFS, 6.7 versus 4.1 months; P = 0.05), but not overall survival (OS, 10.6 versus 9.8 months; P=0.91). KRAS mutations, which were detected in 36% of tumor samples, did not affect the trends of difference in ORR and PFS between C-GEMOX and GEMOX. The two treatment arms had similar adverse events, except that more patients had skin rashes, allergic reactions, and neutropenia in the C-GEMOX arm. Of patients with C-GEMOX, the presence of a grade 2 or 3 skin rash was associated with significantly better ORR, PFS, and OS. Conclusions: Addition of cetuximab did not significantly improve the ORR of GEMOX chemotherapy in ABTC, although a trend of PFS improvement was observed. The trend of improvement did not correlate with KRAS mutation status. ? The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.Biliary tract cancer; Cetuximab; Chemotherapy; KRAS mutation[SDGs]SDG3cetuximab; gemcitabine; oxaliplatin; antineoplastic agent; cetuximab; deoxycytidine; KRAS protein, human; platinum complex; protein p21; adult; advanced cancer; aged; allergy; anorexia; Article; biliary tract cancer; cancer combination chemotherapy; cancer survival; controlled study; diarrhea; dose response; drug dose reduction; drug safety; drug withdrawal; fatigue; female; gene mutation; human; major clinical study; male; nausea; neuropathy; neutropenia; oncogene K ras; oral mucositis; overall survival; phase 2 clinical trial; priority journal; progression free survival; randomized controlled trial; rash; survival rate; survival time; thrombocytopenia; treatment outcome; tumor localization; vomiting; analogs and derivatives; Biliary Tract Neoplasms; clinical trial; comparative study; disease course; disease free survival; drug administration; genetic predisposition; genetics; Kaplan Meier method; middle aged; mortality; multicenter study; mutation; pathology; phenotype; proportional hazards model; Taiwan; time factor; very elderly; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Biliary Tract Neoplasms; Cetuximab; Deoxycytidine; Disease Progression; Disease-Free Survival; Drug Administration Schedule; Female; Genetic Predisposition to Disease; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Mutation; Organoplatinum Compounds; Phenotype; Proportional Hazards Models; Proto-Oncogene Proteins p21(ras); Taiwan; Time Factors; Treatment Outcomejournal article10.1093/annonc/mdv035256320662-s2.0-84929091392