title: Panitumumab in combination with gemcitabine and oxaliplatin does not prolong survival in wild-type KRAS advanced biliary tract cancer: A randomized phase 2 trial (Vecti-BIL study).
abstract: BACKGROUND
  Biliary tract cancer (BTC) is a rare and lethal disease with few therapeutic options. Preclinical data suggest that the epidermal growth factor receptor (EGFR) pathway could be involved in its progression.
  
  
  METHODS
  This open-label, randomized phase 2 trial recruited chemotherapy-naive patients with advanced BTC displaying a wild-type (WT) KRAS status. Patients were randomized to gemcitabine (1000 mg/m(2) ) and oxaliplatin (100 mg/m(2) ) with (arm A) or without (arm B) panitumumab (6 mg/kg) for up to 12 cycles. The primary endpoint was progression-free survival (PFS) analyzed in an intention-to-treat fashion.
  
  
  RESULTS
  Eighty-nine patients (45 in arm A and 44 in arm B) were enrolled between June 2010 and September 2013. After a median follow-up of 10.1 months, the median PFS was 5.3 months (95% confidence interval, 3.3-7.2 months) in arm A and 4.4 months (95% confidence interval, 2.6-6.2 months) in arm B (P = .27). No survival differences were observed: the median overall survival was 9.9 months in arm A and 10.2 months in arm B (P = .42). In a subgroup analysis, no differences in PFS according to the site of the primary tumor were observed; patients with intrahepatic cholangiocarcinoma treated with panitumumab may have had a survival benefit in comparison with the control group (15.1 vs 11.8 months, P = .13). As for safety, skin toxicity was the main adverse event in arm A (80% of the patients). A higher incidence of diarrhea (55.5% vs 31.8%), mucositis (22.2% vs 13.6%), and constipation (24.4% vs 15.9%) was seen in arm A.
  
  
  CONCLUSIONS
  These results confirm the marginal role of anti-EGFR therapy even for WT KRAS-selected BTC.
authors.affiliation: Department of Oncology, University of Turin Medical School/Piedmont Foundation for Oncology, Candiolo Cancer Institute - FPO, IRCCS, Candiolo, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Leone
authors.affiliation: Department of Oncology, University of Turin Medical School/Piedmont Foundation for Oncology, Candiolo Cancer Institute - FPO, IRCCS, Candiolo, Italy.
authors.forename: Donatella
authors.initials: D
authors.lastname: Marino
authors.affiliation: Department of Medical Oncology, San Raffaele Scientific Institute, IRCCS, Milan, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Cereda
authors.affiliation: Department of Oncology, University of Turin Medical School/Piedmont Foundation for Oncology, Candiolo Cancer Institute - FPO, IRCCS, Candiolo, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Filippi
authors.affiliation: Department of Medical Oncology, San Raffaele Scientific Institute, IRCCS, Milan, Italy.
authors.forename: Carmen
authors.initials: C
authors.lastname: Belli
authors.affiliation: Department of Oncology, Medical Oncology 1 Division, Città Della Salute e Della Scienza Hospital and University, Turin, Italy.
authors.forename: Rosella
authors.initials: R
authors.lastname: Spadi
authors.affiliation: Department of Colorectal Oncology, National Cancer Institute G. Pascale Foundation, Naples, Italy.
authors.forename: Guglielmo
authors.initials: G
authors.lastname: Nasti
authors.affiliation: Department of Colorectal Oncology, National Cancer Institute G. Pascale Foundation, Naples, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Montano
authors.affiliation: Niguarda Cancer Center, Niguarda Ca' Granda Hospita, Milan, Italy.
authors.forename: Alessio
authors.initials: A
authors.lastname: Amatu
authors.affiliation: Department of Oncology, University and General Hospital, Udine, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Aprile
authors.affiliation: Department of Oncology, University of Turin Medical School/Piedmont Foundation for Oncology, Candiolo Cancer Institute - FPO, IRCCS, Candiolo, Italy.
authors.forename: Celeste
authors.initials: C
authors.lastname: Cagnazzo
authors.affiliation: Department of Oncology, University and General Hospital, Udine, Italy.
authors.forename: Gianpiero
authors.initials: G
authors.lastname: Fasola
authors.affiliation: Niguarda Cancer Center, Niguarda Ca' Granda Hospita, Milan, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Siena
authors.affiliation: Department of Oncology, Medical Oncology 1 Division, Città Della Salute e Della Scienza Hospital and University, Turin, Italy.
authors.forename: Libero
authors.initials: L
authors.lastname: Ciuffreda
authors.affiliation: Department of Medical Oncology, San Raffaele Scientific Institute, IRCCS, Milan, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Reni
authors.affiliation: Department of Oncology, University of Turin Medical School/Piedmont Foundation for Oncology, Candiolo Cancer Institute - FPO, IRCCS, Candiolo, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Aglietta
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001650:Bile Duct Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D017734:Bile Ducts, Extrahepatic / Q000473:pathology*; D001653:Bile Ducts, Intrahepatic / Q000473:pathology*; D001661:Biliary Tract Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D018281:Cholangiocarcinoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D005260:Female; D005706:Gallbladder Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D000077544:Panitumumab; D011379:Prognosis; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D000911:Antibodies, Monoclonal; C117307:KRAS protein, human; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D003841:Deoxycytidine; D000077544:Panitumumab; C512478:EGFR protein, human; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras); D000093542:Gemcitabine
keywords: KRAS; biliary cancer; chemotherapy; cholangiocarcinoma; gemcitabine and oxaliplatin (GEMOX); panitumumab