Abstract

To investigate the correlation between Kirsten rat sarcoma viral oncogene homolog (KRAS) status and the therapeutic effects of anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (MoAbs) in metastatic colorectal cancer (mCRC). Randomized controlled trials (RCTs) were identified and the association between KRAS mutation and clinical outcome in mCRC patients treated with anti-EGFR MoAbs was investigated. Ten RCTs were included in this meta-analysis. Progression-free survival and overall survival were used to assess the strength of the relationship between KRAS mutation and clinical outcome. In first-line treatment, survival benefit was confined to patients with wild-type KRAS. Chemotherapy regimens and angiogenesis inhibitor treatment influenced the results of the analysis. Wild-type KRAS mCRC patients did not seem to benefit from oxaliplatin-based chemotherapy (PFS: HR = 0.88, 95%CI: 0.70-1.10; OS: HR = 0.93, 95%CI: 0.82-1.04). Clinical benefit in mCRC patients was limited to therapeutic regimens which included anti-EGFR MoAbs and fluorouracil-based therapy (PFS: HR = 0.77, 95%CI: 0.69-0.86; OS: HR = 0.85, 95%CI: 0.75-0.95). When anti-EGFR MoAbs were used as second- or further-line treatment, clinical benefit was still confined to patients with wild-type KRAS. KRAS status is a potential predictive marker of clinical benefit due to anti-EGFR MoAb therapy in mCRC patients.

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