• Javier Martin-Broto, Silvia Stacchiotti, Antonio Lopez-Pousa, Andres Redondo, Daniel Bernabeu, Enrique de Alava, Paolo G Casali, Antoine Italiano, Antonio Gutierrez, David S Moura, Maria Peña-Chilet, Juan Diaz-Martin, Michele Biscuola, Miguel Taron, Paola Collini, Dominique Ranchere-Vince, Garcia Del MuroXavierXCatalan Institute of Oncology, Barcelona, Spain; Institut d'Investigació Biomédica de Bellvitge, University of Barcelona, Barcelona, Spain., Giovanni Grignani, Sarah Dumont, Javier Martinez-Trufero, Emanuela Palmerini, Nadia Hindi, Ana Sebio, Joaquin Dopazo, Angelo Paolo Dei Tos, Axel LeCesne, Jean-Yves Blay, and Josefina Cruz.
• Department of Medical Oncology, University Hospital Virgen del Rocío, Sevilla, Spain; Institute of Biomedicine of Sevilla, Sevilla, Spain. Electronic address: jmartin@mustbesevilla.org.
• Lancet Oncol. 2019 Jan 1; 20 (1): 134-144.

BackgroundA solitary fibrous tumour is a rare soft-tissue tumour with three clinicopathological variants: typical, malignant, and dedifferentiated. Preclinical experiments and retrospective studies have shown different sensitivities of solitary fibrous tumour to chemotherapy and antiangiogenics. We therefore designed a trial to assess the activity of pazopanib in a cohort of patients with malignant or dedifferentiated solitary fibrous tumour. The clinical and translational results are presented here.MethodsIn this single-arm, phase 2 trial, adult patients (aged ≥ 18 years) with histologically confirmed metastatic or unresectable malignant or dedifferentiated solitary fibrous tumour at any location, who had progressed (by RECIST and Choi criteria) in the previous 6 months and had an ECOG performance status of 0-2, were enrolled at 16 third-level hospitals with expertise in sarcoma care in Spain, Italy, and France. Patients received pazopanib 800 mg once daily, taken orally without food, at least 1 h before or 2 h after a meal, until progression or intolerance. The primary endpoint of the study was overall response measured by Choi criteria in the subset of the intention-to-treat population (patients who received at least 1 month of treatment with at least one radiological assessment). All patients who received at least one dose of the study drug were included in the safety analyses. This study is registered with ClinicalTrials.gov, number NCT02066285, and with the European Clinical Trials Database, EudraCT number 2013-005456-15.FindingsFrom June 26, 2014, to Nov 24, 2016, of 40 patients assessed, 36 were enrolled (34 with malignant solitary fibrous tumour and two with dedifferentiated solitary fibrous tumour). Median follow-up was 27 months (IQR 16-31). Based on central radiology review, 18 (51%) of 35 evaluable patients had partial responses, nine (26%) had stable disease, and eight (23%) had progressive disease according to Choi criteria. Further enrolment of patients with dedifferentiated solitary fibrous tumour was stopped after detection of early and fast progressions in a planned interim analysis. 51% (95% CI 34-69) of 35 patients achieved an overall response according to Choi criteria. Ten (29%) of 35 patients died. There were no deaths related to adverse events and the most frequent grade 3 or higher adverse events were hypertension (11 [31%] of 36 patients), neutropenia (four [11%]), increased concentrations of alanine aminotransferase (four [11%]), and increased concentrations of bilirubin (three [8%]).InterpretationTo our knowledge, this is the first trial of pazopanib for treatment of malignant solitary fibrous tumour showing activity in this patient group. The manageable toxicity profile and the activity shown by pazopanib suggests that this drug could be an option for systemic treatment of advanced malignant solitary fibrous tumour, and provides a benchmark for future trials.FundingSpanish Group for Research on Sarcomas (GEIS), Italian Sarcoma Group (ISG), French Sarcoma Group (FSG), GlaxoSmithKline, and Novartis.Copyright © 2019 Elsevier Ltd. All rights reserved.

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