title: An assessment of the benefit-risk balance of FOLFIRINOX in metastatic pancreatic adenocarcinoma.
abstract: BACKGROUND
  We sought to assess the benefit-risk balance of FOLFIRINOX versus gemcitabine in patients with metastatic pancreatic adenocarcinoma.
  
  
  METHODS
  We used generalized pairwise comparisons. This statistical method permits the simultaneous analysis of several prioritized outcome measures. The first priority outcome was survival time (OS). Differences in OS that exceeded two months were considered clinically relevant. The second priority outcome was toxicity. The overall treatment effect was quantified using the net chance of a better outcome, which can be interpreted as the net probability for a random patient treated in the FOLFIRINOX group to have a better overall outcome than a random patient in the gemcitabine group.
  
  
  RESULTS
  In this trial 342 patients received either FOLFIRINOX or gemcitabine. The net chance of a better outcome favored strongly and significantly the FOLFIRINOX group (24.7; P<.001), suggesting a favorable benefit-risk balance of FOLFIRINOX versus gemcitabine. The positive benefit-risk balance of FOLFIRINOX was observed throughout all sensitivity analyses.
  
  
  CONCLUSIONS
  Generalized pairwise comparisons are useful to perform a quantitative assessment of the benefit-risk balance of new treatments. It provides a clinically intuitive way of comparing patients with respect to all important efficacy and toxicity outcomes. Overall the benefit-risk balance of FOLFIRINOX was strongly positive.
authors.affiliation: CNRS, UMR 5558, Laboratoire de Biométrie et Biologie Evolutive, Equipe Biostatistique-Santé, Service de Biostatistiques, Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, 69495 Pierre-Bénite, France.|Medical Oncology Department, Centre Hospitalier Lyon-Sud, Institut de Cancérologie des Hospices Civils de Lyon-IC-HCL, 69495 Pierre-Bénite, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Péron
authors.affiliation: CNRS, UMR 5558, Laboratoire de Biométrie et Biologie Evolutive, Equipe Biostatistique-Santé, Service de Biostatistiques, Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, 69495 Pierre-Bénite, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Roy
authors.affiliation: Institut de Cancérologie de Lorraine, Alexis Vautrin Center, 54500 Vandœuvre-lès-Nancy, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Conroy
authors.affiliation: Medical Oncology Department, Centre Léon Bérard, 69373 Lyon, France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Desseigne
authors.affiliation: Institut Régional du Cancer Montpellier, Val d'Aurelle, 34298 Montpellier, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Ychou
authors.affiliation: Institut Régional du Cancer Montpellier, Val d'Aurelle, 34298 Montpellier, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Gourgou-Bourgade
authors.affiliation: R&D UNICANCER, 75013 Paris, France.
authors.forename: Trevor
authors.initials: T
authors.lastname: Stanbury
authors.affiliation: CNRS, UMR 5558, Laboratoire de Biométrie et Biologie Evolutive, Equipe Biostatistique-Santé, Service de Biostatistiques, Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, 69495 Pierre-Bénite, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Roche
authors.affiliation: CNRS, UMR 5558, Laboratoire de Biométrie et Biologie Evolutive, Equipe Biostatistique-Santé, Service de Biostatistiques, Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, 69495 Pierre-Bénite, France.
authors.forename: Brice
authors.initials: B
authors.lastname: Ozenne
authors.affiliation: International Drug Development Institute (IDDI), San Francisco, CA 94109, USA.
authors.forename: Marc
authors.initials: M
authors.lastname: Buyse
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018450:Disease Progression; D018572:Disease-Free Survival; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D000077146:Irinotecan; D053208:Kaplan-Meier Estimate; D002955:Leucovorin / Q000008:administration & dosage; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D003841:Deoxycytidine; D000077146:Irinotecan; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin; D000093542:Gemcitabine
keywords: benefit-risk assessment; multi-criteria analysis; pancreatic cancer; randomized controlled trial; statistics as topic