Systematic review: Anti- @entity470 treatment effect modification by XXXX mutations in advanced @entity14 .

@entity984 @entity1 @entity14 @entity470
BACKGROUND: @entity984 mutations have been extensively investigated as predictive biomarkers for treatment of advanced @entity14 with the @entity470 ( @entity470 ) antibodies cetuximab and panitumumab. PURPOSE: To summarize whether @entity984 mutation status modifies effects of anti- @entity470 -based treatments for @entity1 with advanced @entity14 and whether @entity984 status predicts clinical outcomes among such @entity1 . DATA SOURCES: MEDLINE and 2 curated genetics databases (through 24 March 2010) were searched for observational studies. MEDLINE, the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, and the Database of Abstracts of Reviews of Effects (through 1 September 2010) were searched for randomized, controlled trials. No search was restricted by language. STUDY SELECTION: Three reviewers screened titles and abstracts to identify published studies assessing @entity984 mutations as predictors of overall and progression-free survival or treatment failure for @entity1 who received anti- @entity470 -based therapy for metastatic @entity14 . DATA EXTRACTION: Three investigators extracted data on population and study-design characteristics, including quality items, and on outcomes of interest. Random-effects meta-analyses were done on nonoverlapping studies. DATA SYNTHESIS: In 4 reanalyses of randomized trials of anti- @entity470 -based therapy versus best supportive care or cytotoxic chemotherapy, no significant benefit was found for overall or progression-free survival from anti- @entity470 -based treatment among @entity984 -positive @entity1 (hazard ratio [HR], 1.0). However, evidence favors anti- @entity470 therapy among @entity984 wild-type @entity1 ; the relative HR across @entity984 -positive and wild-type @entity1 was 1.30 (95% CI, 0.95 to 1.78) for overall survival and 2.22 (CI, 1.74 to 2.84) for progression-free survival by random-effects meta-analysis. In 13 cohorts of @entity1 who received anti- @entity470 antibodies, the summary HR for overall survival was 1.79 (CI, 1.48 to 2.17), with better survival in wild-type @entity1 . The corresponding HR for progression-free survival was 2.11 (CI, 1.74 to 2.55 [16 cohorts]). In random-effects bivariate meta-analysis of 22 studies, the summary sensitivity of @entity984 mutations for predicting lack of response was 0.49 (CI, 0.43 to 0.55), and summary specificity was 0.93 (CI, 0.87 to 0.97). LIMITATIONS: Limited evidence from randomized studies exists. @entity1 -level data are needed to assess modifiers of the mutation-by-treatment interaction. Publication bias could be a concern. CONCLUSION: @entity984 mutations are consistently associated with reduced overall and progression-free survival and increased treatment failure rates among @entity1 with advanced @entity14 treated with anti- @entity470 antibodies. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.
