Article type
Year
Abstract
Background: Anti-epidermal growth factor receptor monoclonal antibodies are approved and effective only in KRAS wild-type patients with advanced colorectal cancer.
Objectives: This meta-epidemiology aimed to compare the reported effect of KRAS mutation status on response to anti-EGFR treatment in metastatic CRC in dataset from randomized controlled trials and the quality of meta-analysis.
Methods: This is a meta-epidemiological study. Meta-analyses of KRAS mutation status that included datasets from at least one observational study and at least one randomized controlled trial were identified through Medline (last update, April 2012). Study-specific hazard ratios or risk ratios were extracted from all identified metaanalyses and synthesized with random effects for (a) all studies, and (b) separately for patients with KRAS wild-type patients and KRAS mutated patients for comparison. RevMan 5.0.24 (Cochrane IMS) has been used for statistical analysis. Prisma checklist for meta-analysis has been used for quality assessment.
Results: Seven eligible meta-analyses were identified. The pooled ratio of risk ratio of patients with wild vs. mutated K-ras showed progression free survival advantage in the addition of anti-EGFR to standard chemotherapy (RRR 0.85 [95% CI, 0.52–1.40]). The overall effect is not significant. There was a great discrepancy with meta-analysis studies. The asymmetric funnel plot suggests that inconsistence is likely existed between meta-analysis of RCT. Most of the meta-analysis studies matched with most items in the Prisma checklist, except the item of assessment on risk of bias.
Conclusions: Evidence from this overview indicates that a great discrepancy on average in the risk estimate of KRAS mutations in advanced colorectal cancer treated with anti-epidermal growth factor receptors.
Objectives: This meta-epidemiology aimed to compare the reported effect of KRAS mutation status on response to anti-EGFR treatment in metastatic CRC in dataset from randomized controlled trials and the quality of meta-analysis.
Methods: This is a meta-epidemiological study. Meta-analyses of KRAS mutation status that included datasets from at least one observational study and at least one randomized controlled trial were identified through Medline (last update, April 2012). Study-specific hazard ratios or risk ratios were extracted from all identified metaanalyses and synthesized with random effects for (a) all studies, and (b) separately for patients with KRAS wild-type patients and KRAS mutated patients for comparison. RevMan 5.0.24 (Cochrane IMS) has been used for statistical analysis. Prisma checklist for meta-analysis has been used for quality assessment.
Results: Seven eligible meta-analyses were identified. The pooled ratio of risk ratio of patients with wild vs. mutated K-ras showed progression free survival advantage in the addition of anti-EGFR to standard chemotherapy (RRR 0.85 [95% CI, 0.52–1.40]). The overall effect is not significant. There was a great discrepancy with meta-analysis studies. The asymmetric funnel plot suggests that inconsistence is likely existed between meta-analysis of RCT. Most of the meta-analysis studies matched with most items in the Prisma checklist, except the item of assessment on risk of bias.
Conclusions: Evidence from this overview indicates that a great discrepancy on average in the risk estimate of KRAS mutations in advanced colorectal cancer treated with anti-epidermal growth factor receptors.