BACKGROUND: @entity12379 , an irreversible ErbB family blocker, is approved for treatment of @entity1 with previously untreated @entity1149 ( @entity1149 ) harboring activating @entity470 ( @entity470 ) mutations. Efficacy of @entity12379 in @entity470 @entity4149 kinase inhibitor-na  ve (TKI-na  ve) @entity1 with uncommon @entity470 mutations (other than exon 19 deletions or exon 21 point mutations) has been reported; however, efficacy in TKI-pretreated @entity1 with uncommon @entity470 mutations is unknown. MATERIALS AND METHODS: In the @entity12379 @entity734 ( @entity734 ), @entity1 with advanced or metastatic, histologically confirmed @entity1149 progressing after at least one line of chemotherapy and one line of @entity470 -TKI treatment were enrolled. Demographic data, mutation type, response rates, time to treatment failure (TTF), and safety in @entity1 harboring uncommon @entity470 mutations were reported. RESULTS: In 60 @entity1 (63% female, median age 63 years [range: 30-84 years]), a total of 66 uncommon @entity470 mutations including 30 @entity9513 mutations were reported (18.4% and 11%, respectively, of known @entity470 mutations within the @entity734 ). Most @entity1 (67%) received @entity12379 as third- or fourth-line treatment. Median TTF was 3.8 months (range: 0.2 to >24.6 months; p = .244) in @entity1 with uncommon mutations compared with 5.1 months (range: 0.1 to >21.1 months) in @entity1 with common mutations (n = 165). Pronounced activity was observed with @entity68902 mutations (TTF >12 months). No new safety signals were detected. CONCLUSION: @entity12379 is clinically active and well tolerated in many TKI-pretreated @entity1149 @entity1 harboring uncommon @entity470 mutations. Compared with results reported in TKI-na  ve @entity1 , activity was also indicated in @entity1 with @entity9513 and exon 20 insertion mutations. IMPLICATIONS FOR PRACTICE: This analysis consists of a large database of @entity1149 @entity1 with uncommon @entity470 mutations who were previously treated with reversible @entity470 @entity4149 kinase inhibitors. Although indirectly assessed, the results indicate that @entity1 with uncommon @entity470 mutations can derive benefit from treatment with the irreversible ErbB family blocker @entity12379 , even in some cases of @entity5 harboring resistance-mediating exon 20 mutations. In this study, adverse events were modest and consistent with previous reports on @entity12379 .

@entity12379 in @entity1149 Harboring Uncommon XXXX Mutations Pretreated With Reversible @entity470 Inhibitors.

@entity1 :: ('9606', 'Species') :: ['patients'] @entity470 :: ('1956', 'Gene') :: ['EGFR', 'epidermal growth factor receptor'] @entity12379 :: ('MESH:C522924', 'Chemical') :: ['Afatinib', 'afatinib'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumors'] @entity1149 :: ('MESH:D002289', 'Disease') :: ['NSCLC', 'non-small cell lung cancer'] @entity68902 :: ('p|SUB|E|709|X', 'ProteinMutation') :: ['E709X'] @entity9513 :: ('p|SUB|T|790|M', 'ProteinMutation') :: ['T790M'] @entity4149 :: ('D014443', 'Chemical') :: ['tyrosine'] @entity734 :: ('MESH:D019966', 'Disease') :: ['CUP', 'compassionate use program']
@entity470 :: (1956,Gene) :: ['EGFR']
