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Masatinib mesylate in imatinib-naive locally advanced or metastatic gastrointestinal stromal tumor (GIST): Results of the French Sarcoma Group phase II trial.

10507 Background: Masitinib mesylate (AB1010, AB Science, Paris, France) is a novel protein tyrosine kinase inhibitor which, in vitro, has greater activity and selectivity than imatinib mesylate against bith wild-type c-Kit receptor and its mutated form in the juxtamembrane region. Masatinib also inhibits PDGFR and FGFR3. This multicenter phase II study evaluated the efficacy and safety of masatinib as a first-line treatment of advanced GIST.


METHODS
Imatinib-naïve patients with inoperable, locally advanced or metastatic GIST received oral masatinib (7.5 mg/kg/day) until progression, refusal or toxicity. A Simon "minimax two stage" design was used. Efficacy variables included response rate at two months, best response according to RECIST, disease control rate (DCR), metabolic response rate and progression free survival (PFS).


RESULTS
30 patients with a median age of 58 years (60% of males) were included from June 2005 to April 2007 in five French institutions. The most frequent relevant grade 3 toxicities were rash (10%), neutropenia (7%) and abdominal pain (7%). One patient presented a grade 4 skin exfoliation. Three patients discontinued treatment due to suspected toxicity. At two months, the response rate was 20% (6/30 patients) according to RECIST (DCR of 98.7%, 29/30 patients) and 84.6% (11/13 evaluable patients) according to FDG-PET response criteria. After a median follow-up of 23.7 months, there were 6.7% of CR, 43.3% of PR, 46.7% of SD and 3.3% of PD as best response (DCR of 96.7%). Mean time to response was 5.7 months (0.8 to 23.3 months). The median PFS was 27.2 months with PFS rates of 68.8% at 1 year and 60.2% at 2 years. Up to date, all but one patient are alive (one patient died of post-surgical complications, unrelated to treatment). Mutational analyses of the patients'tumors are ongoing.


CONCLUSIONS
The results observed with masatinib compare favorably with those reported with imatinib in front-line treatment of advanced GIST both in term of safety and efficacy and support the initiation of a phase III randomized clinical trial. [Table: see text].