Wild-type @entity817 is required for response to panitumumab or cetuximab in metastatic XXXX .

@entity1 @entity984 @entity5 @entity470 @entity2857 @entity8554 @entity817 @entity14 @entity563 @entity1889 @entity1349
PURPOSE Cetuximab or panitumumab are effective in 10% to 20% unselected metastatic @entity14 ( @entity14 ) @entity1 . @entity984 mutations account for approximately 30% to 40% @entity1 who are not responsive. The @entity563 - @entity1889 kinase @entity817 is the principal effector of @entity984 . We hypothesized that, in @entity984 wild-type @entity1 , @entity817 mutations could have a predictive/prognostic value. @entity1 AND METHODS We retrospectively analyzed objective @entity5 responses, time to progression, @entity1349 ( @entity1349 ), and the mutational status of @entity984 and @entity817 in 113 @entity5 from cetuximab- or panitumumab-treated metastatic @entity14 @entity1 . The effect of the @entity817 @entity8554 mutation on cetuximab or panitumumab response was also assessed using cellular models of @entity14 . Results @entity984 mutations were present in 30% of the @entity1 and were associated with resistance to cetuximab or panitumumab (P = .011). The @entity817 @entity8554 mutation was detected in 11 of 79 @entity1 who had wild-type @entity984 . None of the @entity817 -mutated @entity1 responded to treatment, whereas none of the responders carried @entity817 mutations (P = .029). @entity817 -mutated @entity1 had significantly shorter progression-free survival (P = .011) and @entity1349 (P < .0001) than wild-type @entity1 . In @entity14 cells, the introduction of @entity817 @entity8554 allele impaired the therapeutic effect of cetuximab or panitumumab. Treatment with the @entity817 inhibitor @entity2857 restored sensitivity to panitumumab or cetuximab of @entity14 cells carrying the @entity8554 allele. CONCLUSION @entity817 wild-type is required for response to panitumumab or cetuximab and could be used to select @entity1 who are eligible for the treatment. Double-hit therapies aimed at simultaneous inhibition of @entity470 and @entity817 warrant exploration in @entity14 @entity1 carrying the @entity8554 oncogenic mutation.
