Meta-analysis comparing the efficacy of anti-EGFR monoclonal antibody therapy between KRAS G13D and other KRAS mutant metastatic colorectal cancer tumours. (March 2016)

• Record Type: Journal Article
• Authors: Rowland, Andrew; Dias, Mafalda M.; Wiese, Michael D.; Kichenadasse, Ganessan; McKinnon, Ross A.; Karapetis, Christos S.; Sorich, Michael J.
• Is Part Of: European journal of cancer. Volume 55(2016)
• Page Start: 122
• Page End: 130
• Publication Date: 2016-03
• Subjects: KRAS G13D mutation -- metastatic colorectal cancer -- anti-EGFR monoclonal antibodies -- predictive biomarkers.; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Cancer; Tumors; Electronic journals; Periodicals; Electronic journals; 616.994
• DOI: 10.1016/j.ejca.2015.11.025
• Languages: English
• ISSNs: 0959-8049

Abstract

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. 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.