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Lancet Oncol. 2020 Mar;21(3):456-466. doi: 10.1016/S1470-2045(19)30826-5. Epub 2020 Feb 14.

Pazopanib for treatment of typical solitary fibrous tumours: a multicentre, single-arm, phase 2 trial.

Author information

1
Medical Oncology Department, University Hospital Virgen del Rocio, Seville, Spain; Institute of Biomedicine of Seville (University Hospital Virgen del Rocio; Spanish National Research Council; University of Seville), Seville, Spain. Electronic address: jmartin@mustbesevilla.org.
2
Medical Oncology Department, University Hospital of Canarias, Tenerife, Spain.
3
Department of Medical Oncology, Centre Oscar Lambret, Lille Medical School, Lille University, Lille, France.
4
Gustave Roussy, Villejuif, France.
5
Medical Oncology Department, University Hospital Virgen del Rocio, Seville, Spain; Institute of Biomedicine of Seville (University Hospital Virgen del Rocio; Spanish National Research Council; University of Seville), Seville, Spain.
6
Medical Oncology Department, University Hospital Son Espases, Mallorca, Spain.
7
Institute of Biomedicine of Seville (University Hospital Virgen del Rocio; Spanish National Research Council; University of Seville), Seville, Spain.
8
Radiology Department, University Hospital La Paz, Madrid, Spain.
9
Institute of Biomedicine of Seville (University Hospital Virgen del Rocio; Spanish National Research Council; University of Seville), Seville, Spain; Department of Normal and Pathological Cytology and Histology, School of Medicine, University of Seville, Seville, Spain; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Seville, Spain.
10
Laboratory of Molecular Biology, Fundación Instituto Valenciano de Oncología, Valencia, Spain; Department of Basic Medical Sciences, School of Medicine, Catholic University of Valencia San Vicente Martir, Valencia, Spain.
11
Clinical Bioinformatics Area, Fundación Progreso y Salud, University Hospital Virgen del Rocio, Seville, Spain; Bioinformatics in Rare Diseases, Centro de Investigación Biomédica en Red de Enfermedades Raras, Fundación Progreso y Salud, University Hospital Virgen del Rocio, Seville, Spain; Spanish National Bioinformatics Institute, Fundación Progreso y Salud, Hospital Virgen del Rocío, Seville, Spain.
12
Clinical Bioinformatics Area, Fundación Progreso y Salud, University Hospital Virgen del Rocio, Seville, Spain; Bioinformatics in Rare Diseases, Centro de Investigación Biomédica en Red de Enfermedades Raras, Fundación Progreso y Salud, University Hospital Virgen del Rocio, Seville, Spain.
13
Haematology Department, University Hospital Son Espases, Mallorca, Spain.
14
Soft Tissue and Bone Pathology, Histopathology and Pediatric Pathology Unit, Diagnostic Pathology and Laboratory Medicine Department, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Istituto Nazionale Tumori, Milan, Italy.
15
Department of Biopathology Centre Leon Berard, Cancer Research Center of Lyon, Lyon, France.
16
Department of Medical Oncology, University Hospital La Paz, Madrid, Spain.
17
Medical Oncology Department, Sant Pau Hospital, Barcelona, Spain.
18
Division of Medical Oncology, Candiolo Cancer Institute, Candiolo, Italy.
19
Institute of Biomedicine of Seville (University Hospital Virgen del Rocio; Spanish National Research Council; University of Seville), Seville, Spain; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Seville, Spain.
20
Department of Normal and Pathological Cytology and Histology, School of Medicine, University of Seville, Seville, Spain.
21
Laboratory of Molecular Biology, Fundación Instituto Valenciano de Oncología, Valencia, Spain.
22
Cancer Medicine Department, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Istituto Nazionale Tumori, Milan, Italy.
23
Centre Leon Berard, Université de Lyon, Lyon, France.

Abstract

BACKGROUND:

Solitary fibrous tumour is an ultra-rare sarcoma, which encompasses different clinicopathological subgroups. The dedifferentiated subgroup shows an aggressive course with resistance to pazopanib, whereas in the malignant subgroup, pazopanib shows higher activity than in previous studies with chemotherapy. We designed a trial to test pazopanib activity in two different cohorts of solitary fibrous tumour: the malignant-dedifferentiated cohort, which was previously published, and the typical cohort, which is presented here.

METHODS:

In this single-arm, phase 2 trial, adult patients (aged ≥18 years) diagnosed with confirmed metastatic or unresectable typical solitary fibrous tumour of any location, who had progressed in the previous 6 months (by Choi criteria or Response Evaluation Criteria in Solid Tumors [RECIST]) and an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 were enrolled at 11 tertiary hospitals in Italy, France, and Spain. Patients received pazopanib 800 mg once daily, taken orally, until progression, unacceptable toxicity, withdrawal of consent, non-compliance, or a delay in pazopanib administration of longer than 3 weeks. The primary endpoint was proportion of patients achieving an overall response measured by Choi criteria in 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 in ClinicalTrials.gov, NCT02066285, and with the European Clinical Trials Database, EudraCT 2013-005456-15.

FINDINGS:

From June 26, 2014, to Dec 13, 2018, of 40 patients who were assessed, 34 patients were enrolled and 31 patients were included in the response analysis. Median follow-up was 18 months (IQR 14-34), and 18 (58%) of 31 patients had a partial response, 12 (39%) had stable disease, and one (3%) showed progressive disease according to Choi criteria and central review. The proportion of overall response based on Choi criteria was 58% (95% CI 34-69). There were no deaths caused by toxicity, and the most frequent adverse events were diarrhoea (18 [53%] of 34 patients), fatigue (17 [50%]), and hypertension (17 [50%]).

INTERPRETATION:

To our knowledge, this is the first prospective trial of pazopanib for advanced typical solitary fibrous tumour. The manageable toxicity and activity shown by pazopanib in this cohort suggest that this drug could be considered as first-line treatment for advanced typical solitary fibrous tumour.

FUNDING:

Spanish Group for Research on Sarcomas (GEIS), Italian Sarcoma Group (ISG), French Sarcoma Group (FSG), GlaxoSmithKline, and Novartis.

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