1Medical Oncology Department, Oscar Lambret Center, Lille, France2Methodology and Clinical Research Platform, SIRIC OncoLille, Lille, France3Biostatisitics and Methodology Unit, Oscar Lambret Center, Lille, France4Medical Oncology Department, Gustave Roussy, Villejuif, France5Medical Oncology Department, Léon Bérard Center, Lyon, France6Medical Oncology Department, Bergonié Institute, Bordeaux, France7Medical Oncology Department, Paoli-Calmette Institute, Marseille, France8Medical Oncology Department, University Cancer Institute of Toulouse–Oncopole, Toulouse, France9Clinical Research Unit, Oscar Lambret Center, Lille, France10Institute of Pathology, Medical University of Graz, Graz, Austria11Radiology Department, Oscar Lambret Center, Lille, France12General Hospital, Medical University of Vienna, Vienna, Austria
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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.In patients with doxorubicin-pretreated nonadipocytic soft-tissue sarcoma, regorafenib significantly improves quality-adjusted survival in comparison with a placebo (8.0 vs 5.7 mo; P < .001).See also pages 2200-2.