KRAS Testing for Anti-EGFR Therapy in Advanced Colorectal Cancer: An Evidence-Based and Economic Analysis.

摘要: UNLABELLED In February 2010, the Medical Advisory Secretariat (MAS) began work on evidence-based reviews of literature surrounding three pharmacogenomic tests. This project came about when Cancer Care Ontario (CCO) asked MAS to provide analyses effectiveness and cost-effectiveness oncology tests currently in use Ontario.Evidence-based have been prepared for each these technologies. These completed conjunction with internal external stakeholders, including a Provincial Expert Panel Pharmacogenomics (PEPP). Within PEPP, subgroup committees were developed disease area. For technology, an economic analysis was also by Toronto Health Economics Technology Assessment Collaborative (THETA) is summarized within reports.THE FOLLOWING REPORTS CAN BE PUBLICLY ACCESSED AT THE WEBSITE AT: www.health.gov.on.ca/mas or at www.health.gov.on.ca/english/providers/program/mas/mas_about.htmlGENE EXPRESSION PROFILING FOR GUIDING ADJUVANT CHEMOTHERAPY DECISIONS IN WOMEN WITH EARLY BREAST CANCER: An Evidence-Based Economic AnalysisEpidermal Growth Factor Receptor Mutation (EGFR) Testing Prediction Response EGFR-Targeting Tyrosine Kinase Inhibitor (TKI) Drugs Patients Advanced Non-Small-Cell Lung Cancer: AnalysisK-RAS testing Treatment Decisions Colorectal Analysis. OBJECTIVE The objective this systematic review determine predictive value KRAS treatment metastatic colorectal cancer (mCRC) two anti-EGFR agents, cetuximab panitumumab. are being conducted evaluate testing. CLINICAL NEED CONDITION AND TARGET POPULATION Metastatic usually defined as stage IV according American Joint Committee tumour node metastasis (TNM) system D Duke's classification system. advanced either present develop it through progression. (Kristen-RAS, member rat sarcoma virus (ras) gene family oncogenes) frequently mutated epithelial cancers such cancer, mutations occurring mutational hotspots (codons 12 13) protein. Involved EGFR-mediated signalling cellular processes cell proliferation, resistance apoptosis, enhanced motility neoangiogenesis, mutation believed be involved pathogenesis. Such hypothesized targeted (epidermal growth factor receptor tyrosine kinase activity) treatments panitumumab, hence, important evaluating evidence context. MUTATION TESTING ADVANCED COLORECTAL Both panitumumab indicated Canada patients whose tumours WT gene. Cetuximab may offered monotherapy intolerant irinotecan-based chemotherapy who failed both irinotecan oxaliplatin-based regimens received fluoropyrimidine. It can administered combination refractory other regimens. Panitumumab only single agent after failure fluoropyrimidine-, oxaliplatin-, irinotecan-containing Ontario, Eligibility based status their tumour, derived from tissue collected surgical biopsy specimens. that not affected treatments, therefore, whom available testing, additional biopsies prior agents necessary. undergone surgery available, primary site required status. possible sites considered similar. RESEARCH QUESTION To if there guiding decisions therapies chemotherapy. METHODS LITERATURE SEARCH followed its standard procedures May 18, searched following electronic databases: Ovid MEDLINE, EMBASE, MEDLINE In-Process & Other Non-Indexed Citations, Cochrane Central Register Controlled Trials, Database Systematic Reviews International Network Agencies database. subject headings keywords included cetuximab, search further restricted English-language articles published between January 1, 2009 2010 resulting 1335 review. Excluded case reports, comments, editorials, nonsystematic reviews, letters. Studies 2005 December 31, 2008 identified health technology assessment Agency Healthcare Research Quality (AHRQ), 2010. total, 14 observational studies inclusion EBA: 4 monotherapy, 7 cetuximab-irinotecan therapy, 3 INCLUSION CRITERIA articles, English French-language HTAs inclusive.Randomized controlled trials (RCTs) studies, arm include testing.Studies data main outcomes interest, overall progression-free survival.Studies third line chemotherapy.For evaluation, which least 70% study therapy. EXCLUSION entire sample subsequent publications EBA.Studies pediatric populations.Case OUTCOMES OF INTEREST Overall survival (OS), medianProgression-free-survival (PFS), median.Response rates.Adverse event rates.Quality life (QOL). SUMMARY FINDINGS SYSTEMATIC REVIEW: CETUXIMAB OR PANITUMUMAB MONOTHERAPY: Based moderate GRADE evidence, improvement PFS OS favouring without (KRAS wildtype, WT) compared those mutation. CETUXIMAB-IRINOTECAN COMBINATION THERAPY: There low optimize benefits However, discount any effect possibly reversing mutation, observed effects lower than Clinical experts raised concerns biological plausibility observation conclusion would, regarded hypothesis generating. ECONOMIC ANALYSIS Cost-effectiveness budget impact incorporating estimates Evaluation relative cost-effectiveness, decision-analytic cost-utility analysis, assessed genetic versus no context irinotecan, best supportive care. Of importance note focused different options, does assess drug alone. CONCLUSIONS While cost-effective all strategies considered, equally options.