title: Systemic therapy in younger and elderly patients with advanced biliary cancer: sub-analysis of ABC-02 and twelve other prospective trials.
abstract: Outcomes in younger (<40 years) and elderly (≥70 years) patients with advanced biliary cancer (ABC) receiving palliative chemotherapy are unclear. This study assessed outcomes in those receiving monotherapy or combination therapy in thirteen prospective systemic-therapy trials.
  
  
  
  Multivariable analysis explored the impact of therapy on progression-free (PFS) and overall survival (OS) in two separate age cohort groups: <70 years and ≥70 years, and <40 years and ≥40 years.
  
  
  
  Overall, 1163 patients were recruited (Jan 1997-Dec 2013). Median age of entire cohort: 63 years (range 23-85); 36 (3%) were <40, 260 (22%); ≥70. Combination therapy was platinum-based in nine studies. Among patients <40 and ≥70 years, 23 (64%) and 182 (70%) received combination therapy, respectively. Median follow-up was 42 months (95%-CI 37-51). Median PFS for patients <40 and ≥40 years was 3.5 and 5.9 months (P = 0.12), and OS was 10.8 and 9.7 months, respectively (P = 0.55). Median PFS for those <70 and ≥70 years was 6.0 and 5.0 months (P = 0.53), and OS was 10.2 and 8.8 months, respectively (P = 0.08). For the entire cohort, PFS and OS were significantly better in those receiving combination therapy: Hazard Ratio [HR]-0.66, 95%-CI 0.58-0.76, P < 0.0001 and HR-0.72, 95%-CI 0.63-0.82, P < 0.0001, respectively; and in patients ≥70 years: HR-0.54 (95%-CI 0.38-0.77, P = 0.001) and HR-0.60 (95%-CI 0.43-0.85, P = 0.004), respectively. There was no evidence of interaction between age and treatment for PFS (P = 0.58, P = 0.66) or OS (P = 0.18, P = 0.75).
  
  
  
  In ABC, younger patients are rare, and survival in elderly patients in receipt of systemic therapy for advanced disease, whether monotherapy or combination therapy, is similar to that of non-elderly patients, therefore age alone should not influence decisions regarding treatment.
authors.affiliation: Division of Molecular & Clinical Cancer Sciences, Institute of Cancer Sciences, The University of Manchester and The Christie NHS Foundation Trust, Manchester, M20 4BX, UK. Mairead.McNamara@christie.nhs.uk.
authors.forename: Mairéad Geraldine
authors.initials: MG
authors.lastname: McNamara
authors.affiliation: UCL Cancer Institute, London, WCIE 6BT, UK.
authors.forename: John
authors.initials: J
authors.lastname: Bridgewater
authors.affiliation: Cancer Research UK & UCL Cancer Trials Centre, London, WCIE 6BT, UK.
authors.forename: Andre
authors.initials: A
authors.lastname: Lopes
authors.affiliation: Imperial Healthcare, London, WI2 ONN, UK.
authors.forename: Harpreet
authors.initials: H
authors.lastname: Wasan
authors.affiliation: Institute Gustave Roussy, 94805, Villejuif, France.
authors.forename: David
authors.initials: D
authors.lastname: Malka
authors.affiliation: Vejle Hospital, 7100, Vejle, Denmark.
authors.forename: Lars Henrik
authors.initials: LH
authors.lastname: Jensen
authors.affiliation: National Cancer Center Hospital, Tokyo, 104-0045, Japan.
authors.forename: Takuji
authors.initials: T
authors.lastname: Okusaka
authors.affiliation: Princess Margaret Cancer Centre, Toronto, M5G 2M9, Canada.
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Knox
authors.affiliation: Centre Hospitalier Universitaire Vaudois, CH-1011, Lausanne, Switzerland.
authors.forename: Dorothea
authors.initials: D
authors.lastname: Wagner
authors.affiliation: Royal Marsden Hospital, London, UK.
authors.forename: David
authors.initials: D
authors.lastname: Cunningham
authors.affiliation: University of Sydney, Sydney, NSW, 2006, Australia.
authors.forename: Jenny
authors.initials: J
authors.lastname: Shannon
authors.affiliation: Prince of Wales Clinical School, University of New South Wales, Sydney, NSW, 2052, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Goldstein
authors.affiliation: Universitätsmedizin Mainz, 55122, Mainz, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Moehler
authors.affiliation: Mayo Clinic, Phoenix, AZ, 85054, USA.
authors.forename: Tanios
authors.initials: T
authors.lastname: Bekaii-Saab
authors.affiliation: Division of Molecular & Clinical Cancer Sciences, Institute of Cancer Sciences, The University of Manchester and The Christie NHS Foundation Trust, Manchester, M20 4BX, UK.
authors.forename: Juan W
authors.initials: JW
authors.lastname: Valle
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000627:therapeutic use; D001661:Biliary Tract Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D016190:Carboplatin / Q000008:administration & dosage* / Q000627:therapeutic use; D002945:Cisplatin / Q000008:administration & dosage* / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D016190:Carboplatin; D002945:Cisplatin
keywords: Biliary cancer; Elderly; Prospective trials; Systemic therapy; Younger patients