title: Phase II study of gemcitabine, oxaliplatin in combination with panitumumab in KRAS wild-type unresectable or metastatic biliary tract and gallbladder cancer.
abstract: BACKGROUND
  Current data suggest that platinum-based combination therapy is the standard first-line treatment for biliary tract cancer. EGFR inhibition has proven beneficial across a number of gastrointestinal malignancies; and has shown specific advantages among KRAS wild-type genetic subtypes of colon cancer. We report the combination of panitumumab with gemcitabine (GEM) and oxaliplatin (OX) as first-line therapy for KRAS wild-type biliary tract cancer.
  
  
  METHODS
  Patients with histologically confirmed, previously untreated, unresectable or metastatic KRAS wild-type biliary tract or gallbladder adenocarcinoma with ECOG performance status 0-2 were treated with panitumumab 6 mg kg(-1), GEM 1000 mg m(-2) (10 mg m(-2) min(-1)) and OX 85 mg m(-2) on days 1 and 15 of each 28-day cycle. The primary objective was to determine the objective response rate by RECIST criteria v.1.1. Secondary objectives were to evaluate toxicity, progression-free survival (PFS), and overall survival.
  
  
  RESULTS
  Thirty-one patients received at least one cycle of treatment across three institutions, 28 had measurable disease. Response rate was 45% and disease control rate was 90%. Median PFS was 10.6 months (95% CI 5-24 months) and median overall survival 20.3 months (95% CI 9-25 months). The most common grade 3/4 adverse events were anaemia 26%, leukopenia 23%, fatigue 23%, neuropathy 16% and rash 10%.
  
  
  CONCLUSIONS
  The combination of gemcitabine, oxaliplatin and panitumumab in KRAS wild type metastatic biliary tract cancer showed encouraging efficacy, additional efforts of genetic stratification and targeted therapy is warranted in biliary tract cancer.
authors: Division of Hematology/Oncology, James P. Wilmot Cancer Center, University of Rochester, Rochester, NY, USA.
authors: A F
authors: AF
authors: Hezel
authors: Division of Hematology/Oncology, James P. Wilmot Cancer Center, University of Rochester, Rochester, NY, USA.
authors: M S
authors: MS
authors: Noel
authors: Division of Hematology/Oncology, Massachusetts General Hospital, Boston, MA, USA.
authors: J N
authors: JN
authors: Allen
authors: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
authors: T A
authors: TA
authors: Abrams
authors: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
authors: M
authors: M
authors: Yurgelun
authors: Division of Hematology/Oncology, Massachusetts General Hospital, Boston, MA, USA.
authors: J E
authors: JE
authors: Faris
authors: Division of Hematology/Oncology, Massachusetts General Hospital, Boston, MA, USA.
authors: L
authors: L
authors: Goyal
authors: Division of Hematology/Oncology, Massachusetts General Hospital, Boston, MA, USA.
authors: J W
authors: JW
authors: Clark
authors: Division of Hematology/Oncology, Massachusetts General Hospital, Boston, MA, USA.
authors: L S
authors: LS
authors: Blaszkowsky
authors: Division of Hematology/Oncology, Massachusetts General Hospital, Boston, MA, USA.
authors: J E
authors: JE
authors: Murphy
authors: Biostatistics Center, Massachusetts General Hospital, Boston, MA, USA.
authors: H
authors: H
authors: Zheng
authors: Taussig Cancer Institute, Cleveland Clinic Foundation, Cleveland, OH, USA.
authors: A A
authors: AA
authors: Khorana
authors: Division of Hematology/Oncology, James P. Wilmot Cancer Center, University of Rochester, Rochester, NY, USA.
authors: G C
authors: GC
authors: Connolly
authors: Department of Biostatistics and Computational Biology, University of Rochester Medical Center, Rochester, NY, USA.
authors: O
authors: O
authors: Hyrien
authors: Department of Biostatistics and Computational Biology, University of Rochester Medical Center, Rochester, NY, USA.
authors: A
authors: A
authors: Baran
authors: Department of Public Health Sciences, University of Rochester Medical Center, Rochester, NY, USA.
authors: M
authors: M
authors: Herr
authors: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
authors: K
authors: K
authors: Ng
authors: Division of Hematology/Oncology, Massachusetts General Hospital, Boston, MA, USA.
authors: S
authors: S
authors: Sheehan
authors: Division of Hematology/Oncology, Massachusetts General Hospital, Boston, MA, USA.
authors: D J
authors: DJ
authors: Harris
authors: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
authors: E
authors: E
authors: Regan
authors: Department of Pathology, Massachusetts General Hospital, Boston, MA, USA.
authors: D R
authors: DR
authors: Borger
authors: Department of Pathology, Massachusetts General Hospital, Boston, MA, USA.
authors: A J
authors: AJ
authors: Iafrate
authors: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
authors: C
authors: C
authors: Fuchs
authors: Division of Hematology/Oncology, Massachusetts General Hospital, Boston, MA, USA.
authors: D P
authors: DP
authors: Ryan
authors: Division of Hematology/Oncology, Massachusetts General Hospital, Boston, MA, USA.
authors: A X
authors: AX
authors: Zhu
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001661:Biliary Tract Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D005260:Female; D005706:Gallbladder Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D006801:Humans; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D000077544:Panitumumab; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D016896:Treatment Outcome; D018631:ras Proteins / Q000235:genetics; D000093542:Gemcitabine
chemical_list: D000911:Antibodies, Monoclonal; C117307:KRAS protein, human; D009944:Organoplatinum Compounds; D011518:Proto-Oncogene Proteins; D000077150:Oxaliplatin; D003841:Deoxycytidine; D000077544:Panitumumab; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D000093542:Gemcitabine