PURPOSE: To improve the selection of advanced @entity14 @entity1 to panitumumab by optimizing the assessment of RAS ( @entity984 - @entity8497 ) mutations. EXPERIMENTAL DESIGN: Using a centralized pyrosequencing RAS assay, we analyzed the @entity5 of 94 @entity1 , wild-type for @entity984 mutations (codons 12 to 13) by Sanger sequencing (SS), treated with panitumumab. RESULTS: By SS analysis, 94 (62%) of 152 @entity1 were wild-type and their objective response rate to panitumumab was 17%. We first optimized the @entity984 test, by performing an accurate tissue-dissection step followed by pyrosequencing, a more sensitive method, and found further mutations in 12 (12.8%) cases. Secondly, @entity5 were subjected to RAS extension analysis ( @entity984 , exons 3 to 4; @entity8497 exons 2 to 4) by pyrosequencing that allowed to identify several rare mutations: @entity984 codon 61, 5.3%; codon 146, 5.3%; @entity8497 , 9.5%. Overall, RAS mutation rate was 32.9%. All @entity1 with additional RAS mutations had progressive or stable disease, except 3 @entity1 with mutations at codon 61 of @entity984 or @entity8497 who experienced partial (2 cases) or complete response. By excluding from the analysis 11 cases with mutations at codons 61, no @entity1 was responsive to treatment (P=.021). RAS wild-type versus RAS mutated cases had a significantly better time to progression (P=.044), that resulted improved (p=.004) by excluding codon 61 mutations. CONCLUSION: This study shows that by optimizing the RAS test it is possible to significantly improve the identification of @entity1 who do not gain benefit of panitumumab. Prospective studies are warranted to determine the clinical significance of rare mutations.

Optimizing single agent panitumumab therapy in pre-treated advanced XXXX .

@entity1 :: ('9606', 'Species') :: ['patients', 'patient'] @entity984 :: ('3845', 'Gene') :: ['KRAS'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumors'] @entity8497 :: ('4893', 'Gene') :: ['NRAS'] @entity14 :: ('MESH:D015179', 'Disease') :: ['colorectal cancer']
@entity14 :: (MESH:D015179,Disease) :: ['colorectal cancer']
