Predictive factors for outcome in a phase II study of @entity4562 in second-line treatment of advanced @entity418 XXXX .

@entity1 @entity4562 @entity470 @entity984 @entity957 @entity5 @entity22166 @entity418 @entity669 @entity10160
PURPOSE: The efficacy of the @entity470 ( @entity470 ) @entity669 kinase inhibitor (TKI) @entity4562 was assessed in a phase II study in @entity1 with advanced @entity418 . Several biologic features were investigated as potential markers of @entity4562 activity. @entity1 AND METHODS: @entity1 with advanced @entity418 , who had failed one line of prior chemotherapy, were administered @entity4562 500 mg/d. Response was evaluated every 8 weeks. Tumor material obtained before @entity4562 treatment was investigated for gene mutations in @entity470 , @entity984 , and @entity10160 ; protein expression levels of @entity470 , p-Akt, and p- @entity22166 ; and @entity470 gene amplification. RESULTS: Of the 36 enrolled @entity1 , one (2.8%) achieved a partial response, 10 (27.8%) had stable disease, 17 (47.2%) experienced progression on treatment, and eight (22.2%) were not assessable for response. The progression-free survival time was 59 days, and the median overall survival time was 164 days. Although @entity470 or @entity10160 mutations were absent, @entity984 mutations were found in two @entity1 with progressive disease. High @entity470 gene copy number was identified in two @entity1 experiencing partial response or progressive disease. A higher disease control rate (response plus stable disease) was observed in females (P = .038) and in @entity1 with @entity957 ( @entity957 ; P = .013) or high @entity470 expression (P = .002). CONCLUSION: @entity4562 has a modest activity in second-line treatment of advanced @entity418 . However, the @entity1 outcome was significantly better in female @entity1 and in @entity1 demonstrating high @entity470 expression or @entity957 histology. The selection of @entity418 @entity1 for future studies with @entity470 -TKIs based on the level of @entity470 expression in their @entity5 or @entity957 histology should be considered.
