INTRODUCTION: Although @entity1 with @entity1149 ( @entity1149 ) whose @entity5 harbor @entity470 ( @entity470 ) activating mutations commonly experience significant regressions when treated with @entity3866 or @entity4562 , they uniformly develop resistance to these agents. The secondary @entity470 @entity9513 mutation is found in 50% of @entity1 with acquired resistance. Herein, we studied @entity28181 , an oral small molecule inhibitor of multiple receptor @entity669 kinases, including @entity470 , @entity319 , @entity1722 , and @entity25335 , in @entity1149 @entity1 known or suspected of having @entity5 harboring @entity9513 . METHODS: Eligible @entity1 included those with relapsed or recurrent advanced @entity1149 who progressed after >= 12 weeks of stable disease or response to @entity3866 or @entity4562 and/or those @entity1 with a documented @entity470 @entity9513 . @entity28181 300 mg was administered once daily. The primary end point was objective response rate. Pretreatment plasma samples were collected for mutation testing of circulating @entity5 DNA. RESULTS: Forty-one @entity1 were enrolled; 33 were evaluable for efficacy. One partial response was observed (response rate 3% and 90% confidence interval, 0% to 14%). Of @entity1 whose @entity5 harbored @entity9513 , 67% (8/12) had progression of disease as best response compared with 14% (3/21) of those without this mutation. Plasma samples from 40 @entity1 were available for mutation testing, 14 (35%) of which were found to have @entity470 mutations. CONCLUSIONS: The 3% response rate observed did not meet the prespecified threshold to recommend further study of @entity28181 in @entity1 who develop acquired resistance to @entity3866 or @entity4562 . @entity1 with @entity9513 had a significantly worse progression-free survival.

XXXX --a multitargeted @entity669 kinase inhibitor: results of a phase II study in subjects with @entity1149 who have progressed after responding to treatment with either @entity4562 or @entity3866 .

@entity1 :: ('9606', 'Species') :: ['Patients', 'patients'] @entity4562 :: ('MESH:C419708', 'Chemical') :: ['gefitinib'] @entity1722 :: ('2064', 'Gene') :: ['HER2'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'tumors'] @entity470 :: ('1956', 'Gene') :: ['EGFR', 'epidermal growth factor receptor'] @entity1149 :: ('MESH:D002289', 'Disease') :: ['NSCLC', 'non-small cell lung cancer'] @entity319 :: ('3791', 'Gene') :: ['VEGFR2'] @entity25335 :: ('2050', 'Gene') :: ['EphB4'] @entity28181 :: ('MESH:C571826', 'Chemical') :: ['XL647'] @entity669 :: ('CHEBI:18186', 'Chemical') :: ['tyrosine'] @entity9513 :: ('p|SUB|T|790|M', 'ProteinMutation') :: ['T790M'] @entity3866 :: ('MESH:C400278', 'Chemical') :: ['erlotinib']
@entity28181 :: (MESH:C571826,Chemical) :: ['XL647']
