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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
Statement of
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.
RMID: 0030085443
DOI: 10.1016/j.ejca.2015.11.025
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