REGOSARC: Regorafenib versus placebo in doxorubicin-refractory soft-tissue sarcoma-A quality-adjusted time without symptoms of progression or toxicity analysis

Cancer. 2017 Jun 15;123(12):2294-2302. doi: 10.1002/cncr.30661. Epub 2017 Mar 10.


Background: In a placebo-controlled, randomized phase 2 trial ( 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.

Keywords: metastatic soft-tissue sarcoma; placebo; quality-adjusted survival; quality-adjusted time without symptoms of progression or toxicity (Q-TWiST); regorafenib.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Alopecia / chemically induced
  • Anorexia / chemically induced
  • Antineoplastic Agents / therapeutic use*
  • Asthenia / chemically induced
  • Diarrhea / chemically induced
  • Double-Blind Method
  • Fecal Incontinence / chemically induced
  • Female
  • Hand-Foot Syndrome / etiology
  • Hospitalization
  • Humans
  • Hypertension / chemically induced
  • Leiomyosarcoma / drug therapy
  • Liposarcoma / drug therapy
  • Male
  • Middle Aged
  • Mucositis / chemically induced
  • Phenylurea Compounds / therapeutic use*
  • Proportional Hazards Models
  • Pyridines / therapeutic use*
  • Quality of Life
  • Sarcoma / drug therapy*
  • Sarcoma, Synovial / drug therapy
  • Severity of Illness Index
  • Treatment Outcome


  • Antineoplastic Agents
  • Phenylurea Compounds
  • Pyridines
  • regorafenib

Associated data