Epidermal growth factor receptor tyrosine kinase (EGFR-TK) mutation testing in adults with locally advanced or metastatic non-small cell lung cancer: a systematic review and cost-effectiveness analysis

摘要: BACKGROUND: Non-small cell lung cancer (NSCLC) is the most common form of cancer. Some epidermal growth factor receptor tyrosine kinase (EGFR-TK) mutations make tumours responsive to treatment with EGFR-TK inhibitors (EGFR-TKIs) but less standard chemotherapy. Patients NSCLC are therefore tested for tumour gene inform decisions. There a variety tests available detect these mutations. The different vary in specific that they attempt detect, amount cells needed test work, time it takes give result, error rate test, and cost test. OBJECTIVE: To compare performance cost-effectiveness mutation used identify previously untreated adults locally advanced or metastatic NSCLC, who may benefit from first-line TKIs. DATA SOURCES: Twelve databases August 2012 [including MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations Daily Update (OvidSP), EMBASE, Cochrane Database Systematic Reviews (CDSR), Central Register Controlled Trials (CENTRAL), Abstracts Effects (DARE), Health Technology Assessment database (HTA), Science Citation Index (SCI), Latin American Caribbean Sciences Literature (LILACS), BIOSIS Previews, NIHR programme, PROSPERO (International Prospective Reviews)], research registers conference proceedings. A web-based survey gathered data on technical tests. METHODS: Randomised controlled trials were assessed methodological quality using risk bias tool. Diagnostic accuracy studies QUADAS-2. insufficient meta-analysis. For studies, we calculated sensitivity specificity together 95% confidence intervals (CIs). Survival summarised as hazard ratios response relative risks, CIs. health-economic analysis considered long-term costs quality-adjusted life-years (QALYs) associated followed by either chemotherapy TKI. Direct sequencing was taken comparator. de novo model consisted decision tree Markov model. RESULTS: indicated no differences between batch size, turnaround time, number failed samples cost. Six provided testing predicting Estimates similar across studies. analyses clinical effectiveness TKIs compared clear effects reported regardless which EGFR select patients. Cost-effectiveness 'Evidence comparative available' 'Linked evidence' approaches: Therascreen(®) polymerase chain reaction (PCR) Kit (Qiagen, Venlo, Netherlands) both effective costly than direct all exon 19-21 at an incremental ratio £32,167 (comparative) £32,190 (linked) per QALY lost. 'Assumption equal prognostic value' approach: lowest total strategy [commercial-in-confidence (CiC) information has been removed] [Sanger Roche cobas Mutation Testing Kit(®) (Roche Molecular Systems, Inc., Branchburg, NJ, USA)] (CiC removed) expensive (fragment length combined pyrosequencing). LIMITATIONS: assumed outcomes results solely attributable distinguish patients; this assumption ignores other factors might explain variation. CONCLUSION: strong evidence any one had greater Re-testing stored previous where patient already known, could be provide patients mutation-positive mutation-negative tumours, status determined adequate currently unavailable. STUDY REGISTRATION: CRD42012002828. FUNDING: National Institute Research programme.