title: Quality-adjusted survival with combination nal-IRI+5-FU/LV vs 5-FU/LV alone in metastatic pancreatic cancer patients previously treated with gemcitabine-based therapy: a Q-TWiST analysis.
abstract: BACKGROUND
  In the NAPOLI-1 Phase 3 trial, nal-IRI+5-fluorouracil and leucovorin (5-FU/LV) significantly improved median overall survival (6.1 vs 4.2 months, P=0.012) and progression-free survival (3.1 vs 1.5 months, P=0.0001) vs 5-FU/LV alone in metastatic pancreatic adenocarcinoma patients previously treated with gemcitabine-based therapy. This analysis evaluated between treatment differences in quality-adjusted time without symptoms of disease progression or toxicity (Q-TWiST).
  
  
  METHODS
  Overall survival was partitioned into time with grade ⩾3 toxicity (TOX), disease progression (REL), and time without disease progression symptoms or grade ⩾3 toxicity (TWiST). Mean Q-TWiST was calculated by weighting time spent by a utility of 1.0 for TWiST and 0.5 for TOX and REL. In threshold analyses, utility for TOX and REL were varied from 0.0 to 1.0.
  
  
  RESULTS
  Patients in nal-IRI+5-FU/LV (n=117) vs 5-FU/LV (n=119) had significantly more mean time in TWiST (3.4 vs 2.4 months) and TOX (1.0 vs 0.3 months) but similar REL (2.5 vs 2.7 months). In the base case, nal-IRI+5-FU/LV patients had 1.3 months (95% CI, 0.4-2.1; 5.1 vs 3.9) greater Q-TWiST (threshold analyses range: 0.9-1.6 months).
  
  
  CONCLUSIONS
  Within NAPOLI-1, nal-IRI+5-FU/LV resulted in statistically significant and clinically meaningful gains in quality-adjusted survival vs 5-FU/LV alone.
authors.affiliation: Department of Hematology/Oncology/Tumorimmunology, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Pelzer
authors.affiliation: Service d'Hépato-Gastroentérologie et Oncologie Digestive, Hôpital Haut-Lévêque, CHU de Bordeaux, Inserm UMR 1053, Université de Bordeaux, Bordeaux, France.
authors.forename: Jean-Frédéric
authors.initials: JF
authors.lastname: Blanc
authors.affiliation: Digestive Molecular Clinical Oncology Unit, University of Verona, Piazzale L.A. Scuro, 10, 37134 Verona, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Melisi
authors.affiliation: Servicio de Oncologia Médica, Centro Integral Oncológico Clara Campal (CIOCC), Hospital Universitario Madrid Sanchinarro, Calle Oña, 10, 28050 Madrid, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Cubillo
authors.affiliation: Virginia G. Piper Cancer Center at HonorHealth/TGen, 10460N 92nd St #206, Scottsdale, AZ 85258, USA.
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Von Hoff
authors.affiliation: Division of Oncology, Washington University in St Louis, 660 South Euclid Avenue, St Louis, MO 63110, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Wang-Gillam
authors.affiliation: National Institute of Cancer Research, National Health Research Institutes, 2F, No. 367, Sheng-Li Road, Tainan 70456, Taiwan.
authors.forename: Li-Tzong
authors.initials: LT
authors.lastname: Chen
authors.affiliation: Division of Solid Tumor Translational Oncology, DKTK Partner Site Essen, West German Cancer Center, University Hospital Essen, Hufelandstrasse 55, 45147 Essen, Germany.|German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Jens T
authors.initials: JT
authors.lastname: Siveke
authors.affiliation: Pharmerit International, 4350 East-West Hwy #430, Bethesda, MD 20814, USA.
authors.forename: Yin
authors.initials: Y
authors.lastname: Wan
authors.affiliation: Pharmerit International, 4350 East-West Hwy #430, Bethesda, MD 20814, USA.
authors.forename: Caitlyn T
authors.initials: CT
authors.lastname: Solem
authors.affiliation: Pharmerit International, 4350 East-West Hwy #430, Bethesda, MD 20814, USA.
authors.forename: Marc F
authors.initials: MF
authors.lastname: Botteman
authors.affiliation: Shire, Plc, 650 East Kendal St, Cambridge, MA 02142, USA.
authors.forename: Yoojung
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Global Medical Affairs Oncology, Shire GmbH, Zählerweg 10, 6300 Zug, Switzerland.
authors.forename: Floris A
authors.initials: FA
authors.lastname: de Jong
authors.affiliation: Department of Medical Oncology, Christie Hospital NHS Foundation Trust, 550 Wilmslow Rd, Manchester M20 4BX, UK.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Hubner
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D000077146:Irinotecan; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D008081:Liposomes; D008297:Male; D008875:Middle Aged; D053758:Nanoparticles; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D011788:Quality of Life; D019233:Retreatment; D015996:Survival Rate; D000093542:Gemcitabine
chemical_list: D008081:Liposomes; D003841:Deoxycytidine; D000077146:Irinotecan; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin; D000093542:Gemcitabine