Titre :

Nilotinib in locally advanced pigmented villonodular synovitis: a multicentre, open-label, single-arm, phase 2 trial

Auteur(s) :

Gelderblom, Hans [Auteur]
Cropet, Claire [Auteur]
Centre Léon Bérard [Lyon]
Chevreau, Christine [Auteur]
Institut Universitaire du Cancer de Toulouse - Oncopole [IUCT Oncopole - UMR 1037]
Boyle, Richard [Auteur]
Tattersall, Martin [Auteur]
Stacchiotti, Silvia [Auteur]
Italiano, Antoine [Auteur]
Institut Bergonié [Bordeaux]
Piperno-Neumann, Sophie [Auteur]
Institut Curie [Paris]
Le Cesne, Axel [Auteur]
Institut Gustave Roussy [IGR]
Ferraresi, Virginia [Auteur]
Penel, Nicolas [Auteur]
METRICS : Evaluation des technologies de santé et des pratiques médicales - ULR 2694
Duffaud, Florence [Auteur]
Aix Marseille Université [AMU]
Cassier, Philippe Alexandre [Auteur]
Centre Léon Bérard [Lyon]
Toulmonde, Maud [Auteur]
Institut Bergonié [Bordeaux]
Casali, Paolo [Auteur]
Taieb, Sophie [Auteur]
Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] [UNICANCER/Lille]
Guillemaut, Severine [Auteur]
Centre Léon Bérard [Lyon]
Metzger, Severine [Auteur]
Centre Léon Bérard [Lyon]
Perol, David [Auteur]
Centre Léon Bérard [Lyon]
Blay, Jean-Yves [Auteur]
Centre Léon Bérard [Lyon]

Titre de la revue :

The Lancet Oncology

Nom court de la revue :

Lancet Oncol.

Numéro :

19

Pagination :

639-648

Date de publication :

2018-05

ISSN :

1474-5488

Discipline(s) HAL :

Sciences du Vivant [q-bio]

Résumé en anglais : [en]

Pigmented villonodular synovitis (alternatively known as diffuse-type giant cell tumour) is a rare, locally aggressive tumour driven by a specific translocation resulting in the overexpression of colony-stimulating factor ...
Lire la suite >Pigmented villonodular synovitis (alternatively known as diffuse-type giant cell tumour) is a rare, locally aggressive tumour driven by a specific translocation resulting in the overexpression of colony-stimulating factor 1 (CSF1). CSF1 receptor (CSF1R) inhibitors (ie, tyrosine kinase inhibitors and antibodies) induce a response in patients with pigmented villonodular synovitis. We investigated the safety and efficacy of a CSF1R tyrosine kinase inhibitor, nilotinib, in patients with locally advanced non-resectable pigmented villonodular synovitis. In this phase 2, open-label, single-arm study, we enrolled patients from 11 cancer centres of hospitals in four countries (France, Netherlands, Italy, and Australia). Eligible patients were aged at least 18 years with a WHO performance status of 2 or less, and histologically confirmed progressive or relapsing pigmented villonodular synovitis that was inoperable, or resectable only with mutilating surgery. Patients received oral nilotinib (400 mg twice per day) until disease progression, unacceptable toxicity, or completion of 1 year of treatment. The primary endpoint was the proportion of patients who were progression free at 12 weeks, which was centrally assessed according to Response Evaluation Criteria in Solid Tumors version 1.1. Analyses were by modified intention to treat (ie, all patients with no major protocol violations who were treated with nilotinib for at least 3 weeks were included). All participants who received at least one dose of study drug were included in the safety analyses. This study is registered with ClinicalTrials.gov, number NCT01261429, and the results presented here are the final analysis of the trial. Between Dec 15, 2010, and Sept 28, 2012, we enrolled 56 patients with pigmented villonodular synovitis and treated them with nilotinib. Five (9%) patients discontinued study treatment before week 12; therefore, 51 patients were evaluable for the primary endpoint at 12 weeks. The estimated proportion of patients who were progression free at 12 weeks was 92·6% (95% credible interval 84·3-97·9). 54 (96%) of 56 patients had a treatment-related adverse event. Six (11%) of 56 patients had at least one grade 3 treatment-related adverse event (headache, dizziness, and hepatic disorders [n=1], pruritus and toxidermia [n=1], diarrhoea [n=1], increased γ-glutamyl transferase concentration [n=1], anorexia [n=1], and increased headache [n=1]). No grade 4 or 5 adverse events were reported. One patient had a treatment-related serious adverse event (toxidermia) and two patients had serious adverse events not considered to be related to the study drug (borderline ovarian tumour [n=1] and pilonidal cyst excision [n=1]). More than 90% of patients with locally advanced unresectable progressive pigmented villonodular synovitis achieved disease control with 12 weeks of nilotinib treatment. These results indicate that CSF1R tyrosine kinase inhibitors have anti-tumour activity with manageable toxicity in patients with inoperable progressive pigmented villonodular synovitis. Randomised trials investigating the efficacy of nilotinib for patients with unresectable pigmented villonodular synovitis are warranted. Novartis, Institut National du Cancer, EuroSARC, French National Cancer Institute, General Directorate of Care Supply, Lyon Research Innovation for Cancer, L'Agence nationale de la recherche, Laboratory of Excellence, Fondation ARC pour la recherche sur le cancer, Ligue contre le Cancer (comité de l'Ain), Info Sarcomes, and Association DAM'S.Lire moins >

Langue :

Anglais

Audience :

Internationale

Vulgarisation :

Non

Établissement(s) :

CHU Lille
Université de Lille

Collections :

• METRICS : Evaluation des technologies de santé et des pratiques médicales - ULR 2694

Date de dépôt :

2019-12-09T16:49:56Z
2024-05-30T11:14:20Z