Systematic review of pharmacogenetic testing for predicting clinical benefit to anti-EGFR therapy in metastatic colorectal cancer

摘要: Pharmacogenetic testing can help identify patients with metastatic colorectal cancer more likely to respond anti-EGFR therapy. We systematically reviewed the benefits and harms of EGFR-related pharmacogenetic molecular targets downstream KRAS in treatment cancer. searched five electronic databases from January 2000 through November 2010, conducted separate grey literature conference abstracts searches. Two reviewers independently assessed all articles for relevance quality. identified 27 studies, primarily fair- marginal-quality, small retrospective, single-arm cohort studies significant overlap patient populations. seven that studied BRAF independent populations, one NRAS, four PIK3CA, eight PTEN expression, AKT expression. The best evidence BRAF, PIK3CA comes largest retrospective study (n=649) chemorefractory European countries. In this study, mutation was present 6.5% wild-type tumors. Only 8.3% persons mutations, compared 38% without mutations (p=0.0012), responded chemotherapy cetuximab. Clinical sensitivity false positive fraction (1- specificity) were estimated at 9.8% (95% CI 6.3, 14.5) 1.6% 0.2, 5.6), respectively. also associated worse median progression-free survival (absolute difference 18 weeks, p<0.0001), overall 28 p<0.0001). only comparing outcomes who did (n=227) not (n=332) receive cetuximab combination chemotherapy, those had regardless whether or they received Although NRAS exon 20 these is based on a number mutations. Evidence protein expression sparse limited by variable methods assessing Low-quality addressing clinical validity suggests are poorer response outcomes, although association may be EGFR inhibitors.