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Eur J Cancer. 2016 Mar;55:122-30. doi: 10.1016/j.ejca.2015.11.025. Epub 2016 Jan 23.

Meta-analysis comparing the efficacy of anti-EGFR monoclonal antibody therapy between KRAS G13D and other KRAS mutant metastatic colorectal cancer tumours.

Author information

1
Department of Clinical Pharmacology, School of Medicine, Flinders University, Adelaide, 5042, Australia; Flinders Centre for Innovation in Cancer, School of Medicine, Flinders University, Adelaide, 5042, Australia. Electronic address: andrew.rowland@flinders.edu.au.
2
Department of Clinical Pharmacology, School of Medicine, Flinders University, Adelaide, 5042, Australia; School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, 5000, Australia.
3
School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, 5000, Australia.
4
Flinders Centre for Innovation in Cancer, School of Medicine, Flinders University, Adelaide, 5042, Australia.
5
Department of Clinical Pharmacology, School of Medicine, Flinders University, Adelaide, 5042, Australia; Flinders Centre for Innovation in Cancer, School of Medicine, Flinders University, Adelaide, 5042, Australia.

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; anti-EGFR monoclonal antibodies; metastatic colorectal cancer; predictive biomarkers.

PMID:
26812186
DOI:
10.1016/j.ejca.2015.11.025
[Indexed for MEDLINE]

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