title: REGOSARC: Regorafenib versus placebo in doxorubicin-refractory soft-tissue sarcoma-A quality-adjusted time without symptoms of progression or toxicity analysis.
abstract: BACKGROUND
  In a placebo-controlled, randomized phase 2 trial (ClinicalTrials.gov identifier NCT01900743), regorafenib improved progression-free survival (PFS) for patients with doxorubicin-pretreated advanced nonadipocytic sarcoma. A quality-adjusted time without symptoms of progression or toxicity (Q-TWiST) post hoc exploratory analysis was applied to provide an integrated measure of its clinical benefit.
  
  
  METHODS
  In the base-case analysis, each patient's overall survival (OS) was partitioned into 3 mutually exclusive health states: the time with a grade 3 or 4 adverse event (TOX), the time without symptoms of disease or grade 3 or 4 toxicity from treatment, and the time after tumor progression or relapse. The time spent in each state was weighted with a health-state utility associated with that state and was summed to calculate the Q-TWiST. The stability of the base-case analysis was explored with several sensitivity analyses.
  
  
  RESULTS
  In nonadipocytic sarcoma, the PFS was (4.0 months [2.6-5.5 months] with regorafenib vs 1.0 month [0.9-1.8 months] with a placebo; hazard ratio, 0.36 [0.25-0.53]; P < .0001); the OS was 13.4 months (8.6-17.3 months) with regorafenib and 9.0 months (6.8-12.5 months) with a placebo (hazard ratio, 0.67 [0.44-1.02]). With the classic definition of TOX (including all grade 3 and 4 clinical adverse events), the Q-TWiSTs were 8.0 months (7.0-9.0 months) with regorafenib and 5.7 months (4.9-6.4 months) with a placebo (P < .001).
  
  
  CONCLUSIONS
  For patients with doxorubicin-pretreated soft-tissue sarcoma, regorafenib significantly improved quality-adjusted survival in comparison with a placebo. Cancer 2017;123:2294-2302. © 2017 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
authors.affiliation: Medical Oncology Department, Oscar Lambret Center, Lille, France.|Methodology and Clinical Research Platform, SIRIC OncoLille, Lille, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Berry
authors.affiliation: Biostatisitics and Methodology Unit, Oscar Lambret Center, Lille, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Basson
authors.affiliation: Biostatisitics and Methodology Unit, Oscar Lambret Center, Lille, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Bogart
authors.affiliation: Medical Oncology Department, Gustave Roussy, Villejuif, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Mir
authors.affiliation: Medical Oncology Department, Léon Bérard Center, Lyon, France.
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Blay
authors.affiliation: Medical Oncology Department, Bergonié Institute, Bordeaux, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Italiano
authors.affiliation: Medical Oncology Department, Paoli-Calmette Institute, Marseille, France.
authors.forename: François
authors.initials: F
authors.lastname: Bertucci
authors.affiliation: Medical Oncology Department, University Cancer Institute of Toulouse-Oncopole, Toulouse, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Chevreau
authors.affiliation: Methodology and Clinical Research Platform, SIRIC OncoLille, Lille, France.|Clinical Research Unit, Oscar Lambret Center, Lille, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Clisant-Delaine
authors.affiliation: Institute of Pathology, Medical University of Graz, Graz, Austria.
authors.forename: Bernadette
authors.initials: B
authors.lastname: Liegl-Antzager
authors.affiliation: Biostatisitics and Methodology Unit, Oscar Lambret Center, Lille, France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Tresch-Bruneel
authors.affiliation: Biostatisitics and Methodology Unit, Oscar Lambret Center, Lille, France.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Wallet
authors.affiliation: Radiology Department, Oscar Lambret Center, Lille, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Taieb
authors.affiliation: Methodology and Clinical Research Platform, SIRIC OncoLille, Lille, France.|Clinical Research Unit, Oscar Lambret Center, Lille, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Decoupigny
authors.affiliation: Medical Oncology Department, Gustave Roussy, Villejuif, France.
authors.forename: Axel
authors.initials: A
authors.lastname: Le Cesne
authors.affiliation: General Hospital, Medical University of Vienna, Vienna, Austria.
authors.forename: Thomas
authors.initials: T
authors.lastname: Brodowicz
authors.affiliation: Medical Oncology Department, Oscar Lambret Center, Lille, France.|Methodology and Clinical Research Platform, SIRIC OncoLille, Lille, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Penel
mesh_terms: D000368:Aged; D000505:Alopecia / Q000139:chemically induced; D000855:Anorexia / Q000139:chemically induced; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001247:Asthenia / Q000139:chemically induced; D003967:Diarrhea / Q000139:chemically induced; D004311:Double-Blind Method; D005242:Fecal Incontinence / Q000139:chemically induced; D005260:Female; D060831:Hand-Foot Syndrome / Q000209:etiology; D006760:Hospitalization; D006801:Humans; D006973:Hypertension / Q000139:chemically induced; D007890:Leiomyosarcoma / Q000188:drug therapy; D008080:Liposarcoma / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D052016:Mucositis / Q000139:chemically induced; D010671:Phenylurea Compounds / Q000627:therapeutic use*; D016016:Proportional Hazards Models; D011725:Pyridines / Q000627:therapeutic use*; D011788:Quality of Life; D012509:Sarcoma / Q000188:drug therapy*; D013584:Sarcoma, Synovial / Q000188:drug therapy; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D011725:Pyridines; C559147:regorafenib
keywords: metastatic soft-tissue sarcoma; placebo; quality-adjusted survival; quality-adjusted time without symptoms of progression or toxicity (Q-TWiST); regorafenib