title: Phase II study of oral masitinib mesilate in imatinib-naïve patients with locally advanced or metastatic gastro-intestinal stromal tumour (GIST).
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.
  
  
  METHODS
  Imatinib-naïve patients with advanced GIST received oral masitinib at 7.5mg/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.
authors.affiliation: Institut Gustave Roussy, Villejuif, France. lecesne@igr.fr
authors.forename: Axel
authors.initials: A
authors.lastname: Le Cesne
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Blay
authors.forename: Binh Nguyen
authors.initials: BN
authors.lastname: Bui
authors.forename: Olivier
authors.initials: O
authors.lastname: Bouché
authors.forename: Antoine
authors.initials: A
authors.lastname: Adenis
authors.forename: Julien
authors.initials: J
authors.lastname: Domont
authors.forename: Angela
authors.initials: A
authors.lastname: Cioffi
authors.forename: Isabelle
authors.initials: I
authors.lastname: Ray-Coquard
authors.forename: Nathalie
authors.initials: N
authors.lastname: Lassau
authors.forename: Sylvie
authors.initials: S
authors.lastname: Bonvalot
authors.forename: Alain
authors.initials: A
authors.lastname: Moussy
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Kinet
authors.forename: Olivier
authors.initials: O
authors.lastname: Hermine
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001549:Benzamides; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D005260:Female; D005602:France; D046152:Gastrointestinal Stromal Tumors / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D006801:Humans; D000068877:Imatinib Mesylate; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects; D010880:Piperidines; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D011725:Pyridines; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects; D013844:Thiazoles / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D010880:Piperidines; D011725:Pyridines; D011743:Pyrimidines; D013844:Thiazoles; D000068877:Imatinib Mesylate; D019009:Proto-Oncogene Proteins c-kit; C526575:masitinib