Highlights
- •No significant difference in the efficacy of anti-EGFR mAb therapy for metastatic colorectal cancer (mCRC) between KRAS G13D and other KRAS mutations.
- •Continued screening for KRAS G13D mutations is supported.
- •The use of anti-EGFR mAbs should remain limited to RAS wild-type mCRC tumours.
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
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Article info
Publication history
Published online: January 25, 2016
Accepted:
November 29,
2015
Received in revised form:
November 23,
2015
Received:
October 21,
2015
Footnotes
☆Funding: This work was funded by a grant from the National Health and Medical Research Council of Australia (Grant ID# 1085364).
Identification
Copyright
© 2015 Elsevier Ltd. Published by Elsevier Inc. All rights reserved.
