Regosarc: regorafenib versus placebo in doxorubicin-refractory soft-tissue sarcoma-a quality-adjusted time without symptoms of progression or toxicity analysis
Résumé
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.
Mots clés
Mesh:Severity of Illness Index
Mesh:Sarcoma
Mesh:Synovial/drug therapy
Mesh:Sarcoma/drug therapy*
Mesh:Quality of Life
Mesh:Male
Mesh:Middle Aged
Mesh:Mucositis/chemically induced
Mesh:Phenylurea Compounds/therapeutic use*
Mesh:Proportional Hazards Models
Mesh:Pyridines/therapeutic use*
Mesh:Leiomyosarcoma/drug therapy
Mesh:Aged
Mesh:Alopecia/chemically induced
Mesh:Anorexia/chemically induced
Mesh:Antineoplastic Agents/therapeutic use*
Mesh:Asthenia/chemically induced
Mesh:Diarrhea/chemically induced
Mesh:Double-Blind Method
Mesh:Fecal Incontinence/chemically induced
Mesh:Female
Mesh:Hand-Foot Syndrome/etiology
Mesh:Hospitalization
Mesh:Humans
quality-adjusted time without symptoms of progression or toxicity (Q-TWiST)
metastatic soft-tissue sarcoma
placebo
quality-adjusted survival
regorafenib
Mesh:Hypertension/chemically induced
Mesh:Liposarcoma/drug therapy
Mesh:Treatment Outcome
Domaines
Sciences du Vivant [q-bio]| Origine | Accord explicite pour ce dépôt |
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