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

• Published in: European journal of cancer (1990) Vol. 46; no. 8; pp. 1344 - 1351
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 01.05.2010; Elsevier
• Subjects: Administration, Oral; Adult; Aged; Aged, 80 and over; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - adverse effects; Benzamides; Biological and medical sciences; c-Kit; Cell survival; Disease-Free Survival; Dose-Response Relationship, Drug; Female; France; Gastrointestinal Stromal Tumors - drug therapy; Gastrointestinal Stromal Tumors - genetics; Gastrointestinal Stromal Tumors - pathology; GIST; Hematology, Oncology and Palliative Medicine; Humans; Imatinib; Imatinib Mesylate; Locally advanced gastro-intestinal stromal tumour; Male; Masitinib; Medical sciences; Metastatic gastro-intestinal stromal tumour; Middle Aged; Pharmacology. Drug treatments; Phase 2 study; Piperazines - administration & dosage; Piperazines - adverse effects; Proto-Oncogene Proteins c-kit - genetics; Pyrimidines - administration & dosage; Pyrimidines - adverse effects; Thiazoles - administration & dosage; Thiazoles - adverse effects; Treatment Outcome; Tumors; Tyrosine kinase inhibitor; France; Imatinib; GIST; Phase 2 study; c-Kit; Locally advanced gastro-intestinal stromal tumour; Tyrosine kinase inhibitor; Masitinib; Metastatic gastro-intestinal stromal tumour; Antineoplastic agent; Metastasis; Gastrointestinal stromal tumor; Cancerology; Phase II trial; Intestinal disease; Advanced stage; kit Gene; Protein-tyrosine kinase; Protooncogene; Human; Enzyme; Transferases; Enzyme inhibitor; Malignant tumor; Mesilate; Treatment; C-Onc gene; Digestive diseases; Locally advanced stage; Cancer
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/j.ejca.2010.02.014

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 7.5 mg/kg/d. Efficacy end-points included response rate (RR) at 2 months, 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 34 months. The most frequent grade 3–4 toxicities were rash (10%) and neutropaenia (7%). Two patients withdrew due to treatment-related adverse events. At 2 months, 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 5.6 months (0.8–23.8 months). Estimated median PFS was 41.3 months with PFS rate of 59.7% [37.9; 76.0] and 55.4 [33.9; 72.5] at 2 and 3 years, respectively. The OS at 2 and 3 years 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.