Schilder RJ et al. - In a trial to assess the activity and tolerability of an oral dose of imatinib mesylate in pts with recurrent or persistent epithelial ovarian or primary peritoneal carcinoma to investigate the association between expression of certain markers and clinical outcome, it was found that imatinib mesylate was well tolerated but had minimal single-agent activity in pts with recurrent ovarian or primary peritoneal carcinoma. No marker was identified to predict activity of imatinib; however, tumor p-AKT and plasma vascular endothelial growth factor (VEGF) levels were associated with poor outcome Methods
Primary measure of clinical efficacy was progression-free survival (PFS) at 6 months
Mutational analysis of KIT, immunohistochemistry (IHC), and enzyme-linked immunosorbent assay for markers (KIT, platelet-derived growth factor [PDGF] receptor [-R], AKT2, phosphorylated AKT [p-AKT], stem cell factor [SCF], and PDGF) were performed
Results
56 eligible pts were evaluated; 9 were progression free for at least 6 months including 1 complete responder
Median PFS and survival were 2 and 16 months, respectively
Most common grade 3 and 4 toxicities were neutropenia, GI, dermatologic effects, pain, and electrolyte disturbances
At least 1 target of imatinib was expressed in all tumors, and most tumors expressed all 3 receptors
Higher expression of p-AKT and PDGFR-β were associated with shorter PFS, and higher IHC scores of SCF and p-AKT were associated with decreased overall survival
No sequence mutations were detected in the KIT gene
Higher pretreatment plasma concentrations of PDGF-AB, PDGF-BB, and VEGF were individually associated with shorter PFS and survival
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