Phase II study of oral masitinib mesilate in imatinib-naïve patients with locally advanced or metastatic gastro-intestinal stromal tumour (GIST)

Le Cesne, Axel; Blay, Jean-Yves; Bui, Binh Nguyen; Bouché, Olivier; Adenis, Antoine; Domont, Julien; Cioffi, Angela; Ray-Coquard, Isabelle; Lassau, Nathalie; Bonvalot, Sylvie; Moussy, Alain; Kinet, Jean-Pierre; Hermine, Olivier

doi:10.1016/j.ejca.2010.02.014

« Previous Next »European Journal of Cancer
Volume 46, Issue 8 , Pages 1344-1351, May 2010

Phase II study of oral masitinib mesilate in imatinib-naïve patients with locally advanced or metastatic gastro-intestinal stromal tumour (GIST)☆

Axel Le Cesne
- Institut Gustave Roussy, Villejuif, France
- Corresponding author: Oncologie Médicale, Institut Gustave Roussy, 26 rue Camille Desmoulins, 94805 Villejuif, France. Tel.: +33 (0) 1 42 11 43 16; fax: +33 (0) 1 42 11 52 19.
Jean-Yves Blay
- Hôpital Edouard Herriot and INSERM U453, Centre Léon Bérard, Lyon, France
Binh Nguyen Bui
- Institut Bergonié, Bordeaux, France
Olivier Bouché
- CHU Reims, Hôpital Robert Debré, Reims, France
Antoine Adenis
- Centre Oscar Lambret, Lille, France
Julien Domont
- Institut Gustave Roussy, Villejuif, France
Angela Cioffi
- Institut Gustave Roussy, Villejuif, France
Isabelle Ray-Coquard
- Hôpital Edouard Herriot and INSERM U453, Centre Léon Bérard, Lyon, France
Nathalie Lassau
- Institut Gustave Roussy, Villejuif, France
Sylvie Bonvalot
- Institut Gustave Roussy, Villejuif, France
Alain Moussy
- AB Science, SA, Paris, France
Jean-Pierre Kinet
- Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA
Olivier Hermine
- Service d’Hematologie, CNRS, UMR 8147, Centre de référence des mastocytoses, Université Paris V René Descartes, Hôpital Necker, Paris, France

Received 6 November 2009; received in revised form 1 February 2010; accepted 9 February 2010. published online 08 March 2010.

Abstract

Background

Masitinib is a tyrosine kinase inhibitor with greater in vitro activity and selectivity for the wild-type c-Kit receptor and its juxtamembrane mutation than imatinib, without inhibiting kinases of known toxicities. This phase II study evaluated masitinib as a first-line treatment of advanced GIST.

Patients and methods

Imatinib-naïve patients with advanced GIST received oral masitinib at 7.5mg/kg/d. Efficacy end-points included response rate (RR) at 2months, best response according to RECIST, metabolic response rate, disease control rate (DCR), progression-free survival (PFS) and overall survival rate (OS).

Results

Thirty patients were enrolled with a median follow-up of 34months. The most frequent grade 3–4 toxicities were rash (10%) and neutropaenia (7%). Two patients withdrew due to treatment-related adverse events. At 2months, RR was 20% according to response evaluation criteria in solid tumours (RECIST) and 86% according to FDG-PET response criteria. Best responses were a complete response in 1/30 patient (3.3%), partial response in 15/30 patients (50%), stable disease in 13/30 patients (43.3%) and progressive disease in 1/30 patient (3.3%); (DCR: 96.7%). Median time-to-response was 5.6months (0.8–23.8months). Estimated median PFS was 41.3months with PFS rate of 59.7% [37.9; 76.0] and 55.4 [33.9; 72.5] at 2 and 3years, respectively. The OS at 2 and 3years was stable at 89.9% [71.8; 96.6].

Conclusions

Masitinib appears to be effective as a first-line treatment of advanced GIST with comparable results to imatinib in terms of safety and response. PFS and in particular OS data show promise that masitinib may provide sustainable benefits. There is sufficient compelling evidence to warrant a phase III clinical trial.

Keywords: Masitinib, c-Kit, Imatinib, Locally advanced gastro-intestinal stromal tumour, Metastatic gastro-intestinal stromal tumour, GIST, Tyrosine kinase inhibitor, Phase 2 study