- •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.
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.
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).
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.
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.
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Published online: January 25, 2016
Accepted: November 29, 2015
Received in revised form: November 23, 2015
Received: October 21, 2015
☆Funding: This work was funded by a grant from the National Health and Medical Research Council of Australia (Grant ID# 1085364).
© 2015 Elsevier Ltd. Published by Elsevier Inc. All rights reserved.