Molecular characteristics predict clinical outcomes: prospective trial correlating response to the XXXX tyrosine kinase inhibitor @entity4562 with the presence of sensitizing mutations in the tyrosine binding domain of the @entity470 gene.

@entity1 @entity4562 @entity5 @entity470 @entity984 @entity1149 @entity133
PURPOSE: To determine if @entity5 regression following treatment with @entity4562 correlates with the presence of sensitizing mutations in @entity470 ( @entity470 ). @entity1 AND METHODS: @entity1 with resectable stage I and II @entity1149 ( @entity1149 ) enriched for the likelihood of @entity470 mutation ( <= 15 pack-year cigarette smoking history and/or a component of @entity133 ) received preoperative @entity4562 for 21 days. Tumor specimens were analyzed for @entity470 and @entity984 mutations and @entity470 protein expression and amplification. @entity1 with 25% or more reduction in @entity5 size measured bidimensionally at 3 weeks and/or @entity1 with an @entity470 mutation received adjuvant @entity4562 for 2 years postoperatively. RESULTS: Fifty @entity1 with stage I/II @entity1149 were treated. After 21 days of preoperative @entity4562 a response of 25% or more was observed in 21 of 50 (42%) @entity1 . Seventeen of 21 @entity1 with a response had an @entity470 mutation and 4 of 21 @entity1 with a response did not (P = 0.0001). Twenty-five of 50 @entity1 were eligible to receive adjuvant @entity4562 . With a median follow-up of 44.1 months, 2-year disease free survival for @entity470 mutant @entity1 and for those who received adjuvant @entity4562 was not statistically different than those who were @entity470 wild-type and those who did not receive adjuvant @entity4562 . The median disease free and overall survivals have not been reached. CONCLUSIONS: The presence of sensitizing @entity470 mutations correlates with radiographic response. A short course of preoperative treatment serves a platform for evaluating activity of new agents and assures sufficient @entity5 availability for correlative analyses.
