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Lancet Oncol. 2016 Dec;17(12):1732-1742. doi: 10.1016/S1470-2045(16)30507-1. Epub 2016 Oct 14.

Safety and efficacy of regorafenib in patients with advanced soft tissue sarcoma (REGOSARC): a randomised, double-blind, placebo-controlled, phase 2 trial.

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Medical Oncology Department, Gustave Roussy, Villejuif, France.
Medical University Vienna, General Hospital, Vienna, Austria.
Medical Oncology Department, Institut Bergonié, Bordeaux, France.
Biostatisitics and Methodology Unit, Centre Oscar Lambret, Lille, France.
Medical Oncology Department, Centre Léon Bérard, Lyon, France.
Medical Oncology Department, Institut Paoli-Calmette, Marseille, France.
Medical Oncology Department, Institut Universitaire de Cancérologie de Toulouse, Oncopôle, Toulouse, France.
Medical Oncology Department, Institut Curie, Paris, France.
Medical Oncology Department, René Gauducheau, Saint-Herblain, France.
Medical Oncology Department, CH La Timone, Marseille, France.
Medical Oncology Department, Centre Eugène Marquis, Rennes, France.
Medical Oncology Department, Centre François Baclesse, Caen, France.
Institute of Pathology, Medical University of Graz, Graz, Austria.
Clinical Resarch Unit, Centre Oscar Lambret and Methodology and Clinical Research Platform of SIRIC OncoLille, Lille, France.
Radiology Department, Centre Oscar Lambret, Lille, France.
Medical Oncology Department, Centre Henri Becquerel, Rouen France.
Medical Oncology Department, Centre Alexis Vautrin, Nancy, France.
Medical Oncology Department, Institut de Cancérologie de la Loire Lucien Neuwirth, St Priest En Jarez, France.
Medical Oncology Department, Centre René Huguenin, Saint-Cloud, France.
Medical Oncology Department, Institut de Cancérologie de Montpellier; Montpellier, France.
Medical Oncology Department, Centre Antoine Lacassagne, Nice, France.
Medical Oncology Department, Hopital Saint-Louis, Paris, France.
Medical Oncology Department, Universitätsklinik für Innere Medizin I, Innsbruck, Austria.
Medical Oncology Department, Centre GF Leclerq, Dijon, France.
Medical Oncology Department, Hopital Saint-Jacques, Besançon, France; Medical Oncology department, Centre Oscar Lambret, Lille, France.
Methodology and Clinical Research Platform of SIRIC OncoLille, Lille, France. Electronic address:



Regorafenib is a multikinase inhibitor with proven activity in refractory gastrointestinal stromal tumours and chemotherapy-refractory advanced colorectal cancers. We assessed this agent's efficacy and safety in patients with metastatic soft tissue sarcomas previously treated with anthracycline.


In this randomised, double-blind, phase 2 trial undertaken in France and Austria, we enrolled patients aged 18 years and older with advanced soft tissue sarcomas who had received previous doxorubicin or other anthracycline treatment. These patients were randomly assigned (1:1) into one of the following four cohorts: liposarcoma, leiomyosarcoma, synovial sarcoma, and other sarcomas. Participants were treated with oral regorafenib (160 mg per day 3 weeks on and 1 week off) or matched placebo. Patients receiving placebo were offered optional crossover in case of centrally confirmed disease progression. The random allocation schedule was computer-generated with permuted blocks of four patients, with two stratification factors: country (France or Austria) and previous exposure to pazopanib (yes or no). Eligibility criteria included patients with histologically proven advanced and inoperable soft tissue sarcomas with intolerance or failure to doxorubicin or other anthracycline-based chemotherapy and at least one unidimensionally or bidimensionally measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST; version 1.1). The primary endpoint was RECIST-based progression-free survival after central radiological review in the intention-to-treat population. Patients, physicians, and radiologists of the panel were masked to treatment allocation. This study is still open for recruitment for an additional stratum (patients previously treated with pazopanib) and registered with, NCT01900743.


From Aug 5, 2013, to Nov 26, 2014, 182 patients were randomly assigned to one of four cohorts and included in the final analysis. At the cutoff date (Jan 7, 2016), the number of required events was reached for the four cohorts. In the liposarcoma cohort, progression-free survival was 1·1 months (95% CI 0·9-2·3) with regorafenib versus 1·7 months (0·9-1·8) with placebo (HR 0·89 [95% CI 0·48-1·64] p=0·70). In the leiomyosarcoma cohort, progression-free survival was 3·7 months (95% CI 2·5-5·0) with regorafenib versus 1·8 (1·0-2·8) months with placebo (HR 0·46 [95% CI 0·46-0·80] p=0·0045). In the synovial sarcoma cohort, progression-free survival was 5·6 months (95% CI 1·4-11·6) with regorafenib versus 1·0 (0·8-1·4) with placebo (HR 0·10 [95% CI 0·03-0·35] p<0·0001). In the other sarcoma cohort, progression-free survival was 2·9 months (95% CI 1·0-7·8) with regorafenib versus 1·0 (0·9-1·9) with placebo (HR 0·46 [95% CI 0·25-0·81] p=0·0061). Before crossover, the most common clinically significant grade 3 or higher adverse events were arterial hypertension (17 [19%] events in the 89 patients in the regorafenib group vs two [2%] events in the 92 patients in the placebo group), hand and foot skin reaction (14 [15%] vs no events) and asthenia (12 [13%] vs six [6%]). One treatment-related death occurred in the regorafenib group due to liver failure.


Regorafenib has an important clinical antitumour effect in non-adipocytic soft tissue sarcomas, improving progression-free survival. Regorafenib should be further evaluated in this setting, and its therapeutic role has to be defined in the context of the growing therapeutic armamentarium, already including one approved multikinase inhibitor, pazopanib.


Bayer HealthCare.

[Indexed for MEDLINE]

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