Clinical benefit of imatinib in patients (pts) with metastatic gastrointestinal stromal tumors (GIST) negative for the expression of CD117 in the S0033 trial.

9010 Background: IM is effective in the majority of pts with GIST, but limited data exist on KIT- GIST. S0033 aimed to evaluate differences between two initial dose levels of IM (400 vs. 800 mg/day) in pts with GIST expressing CD117 (KIT+), a subset of pts with KIT- GIST were treated. This abstract describes the outcomes of these pts and compares them with the KIT+ pts treated.,Central pathology review was performed by a single pathologist on tumor specimens retrospectively, and data from S0033 (746 pts randomized) was analyzed. Pre-treatment tumor samples from 344 pts were also examined for mutations of KIT or PDGFRA.,Pathology has been reviewed on 414 pts: 377 (91%) had KIT+ GIST, 14 (3%) KIT- GIST, and 16 (4%) leiomyosarcoma/other subtype. Eight of the KIT- GISTs were genotyped and mutations in KIT or PDGFRA were noted in 4 and 3, respectively. (mutation frequency 87.5% for KIT- GISTs). Twelve non-GIST sarcomas had no mutations. The response rate and PFS in the pts with KIT- GISTs was not significantly different than that seen in KIT+ GISTs (43% vs. 49%, estimated PFS at 2 yrs). Pts with leiomyosarcoma or other histology have a significantly worse outcome than either KIT+ or KIT- GIST pts, with PFS 13% at 2 yrs and a median survival of about eight months compared to GIST pts for whom median survival has still not been reached. A significant difference in overall survival was noted in favor of the KIT+ GIST vs. KIT- GIST (77% vs. 57%, estimated OS at 2 yrs, p<0.01), although this was an unplanned subset analysis. Toxicities of all grades were similar across in the various histological groups.,Our results indicate that IM therapy can provide clinical benefit for pts with KIT- GIST. The high incidence of kinase mutations in KIT- GIST support a therapeutic trial of IM for all GIST pts regardless of CD117 expression. There is no evidence of significant activity with IM for the non-GIST malignancies treated on this study. [Table: see text].