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https://hdl.handle.net/2440/112145
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Type: | Journal article |
Title: | Meta-analysis comparing the efficacy of anti-EGFR monoclonal antibody therapy between KRAS G13D and other KRAS mutant metastatic colorectal cancer tumours |
Author: | Rowland, A. Dias, M. Wiese, M. Kichenadasse, G. McKinnon, R. Karapetis, C. Sorich, M. |
Citation: | European Journal of Cancer, 2016; 55:122-130 |
Publisher: | Elsevier |
Issue Date: | 2016 |
ISSN: | 0959-8049 1879-0852 |
Statement of Responsibility: | Andrew Rowland, Mafalda M.Dias, Michael D.Wiese, Ganessan Kichenadasse, Ross A.McKinnon, Christos S.Karapetis Michael J.Sorich |
Abstract: | Background: Metastatic colorectal cancer (mCRC) tumours harbouring a RAS mutation are associated with a lack of treatment benefit from anti-EGFR monoclonal antibodies (mAbs). However, observational evidence has led to speculation that mCRC patients with KRAS G13D mutant (MT) tumours may derive a benefit from treatment with anti-EGFR mAbs. Methods: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate whether the efficacy of anti-EGFR mAbs for mCRC differs between tumours harbouring a KRAS G13D mutation (KRAS G13D) and KRAS mutations other than G13D (other KRAS MT). Results: Eight RCTs (n = 5967) met the inclusion criteria for assessment of both overall survival (OS) and progression-free survival (PFS). For other KRAS MT the hazard ratio for OS benefit with addition of anti-EGFR mAb therapy was 1.06 (95% confidence interval [CI]; 0.96, 1.17), compared to 1.08 (95% CI; 0.73, 1.60) for KRAS G13D [test for interaction p = 0.99]. In contrast, the hazard ratio for KRAS wild-type (WT) tumours was 0.85 (95% CI; 0.76, 0.95). Regarding PFS benefit with anti-EGFR mAbs, the hazard ratio was 1.07 (95% CI; 0.92, 1.26) for other KRAS MT, 0.96 (95% CI; 0.73, 1.27) for KRAS G13D, and 0.68 (95% CI; 0.54, 0.85) for KRAS WT. Again, the test for interaction (p = 0.46) demonstrated no significant difference in PFS benefit for anti-EGFR mAb therapy between KRAS G13D and other KRAS MT. Conclusion: This meta-analysis demonstrates no significant difference between KRAS G13D and other KRAS MT tumours in terms of treatment benefit from anti-EGFR mAbs for mCRC. |
Keywords: | KRAS G13D mutation; metastatic colorectal cancer; anti-EGFR monoclonal antibodies; predictive biomarkers |
Rights: | © 2015 Elsevier Ltd. All rights reserved. |
DOI: | 10.1016/j.ejca.2015.11.025 |
Grant ID: | http://purl.org/au-research/grants/nhmrc/1085364 |
Published version: | http://dx.doi.org/10.1016/j.ejca.2015.11.025 |
Appears in Collections: | Aurora harvest 3 Public Health publications |
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