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BRAF V600E mutation and resistance to anti-EGFR monoclonal antibodies in patients with metastatic colorectal cancer: a meta-analysis

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Abstract

Epidemiologic studies have evaluated the association between BRAF mutations and resistance to the treatment of anti-EGFR monoclonal antibodies (MoAb) in patients with metastatic colorectal cancer (mCRC). However, the results are still inconclusive. To derive a more precise estimation of the relationship, we performed this meta-analysis. A total of 11 studies were included in the final meta-analysis. There were seven studies for unselected mCRC patients and four studies for patients with wild type KRAS mCRC. Among unselected mCRC patients, BRAF V600E mutation was detected in 48 of 546 primary tumors (8.8%). The objective response rate (ORR) of patients with mutant BRAF was 29.2% (14/48), whereas the ORR of patients with wild-type BRAF was 33.5% (158/472).The overall RR for ORR of mutant BRAF patients over wild-type BRAF patients was 0.86 (95% CI = 0.57–1.30; P = 0.48). For patients with KRAS wild-type mCRC, BRAF V600E mutation was detected in 40 of 376 primary tumors (10.6%). The ORR of patients with mutant BRAF was 0.0% (0/40), whereas the ORR of patients with wild-type BRAF was 36.3% (122/336). The pooled RR of mutant BRAF patients over wild-type BRAF patients was 0.14 (95% CI = 0.04–0.53; P = 0.004). In conclusion, this meta-analysis provides evidence that BRAF V600E mutation is associated with lack of response in wild-type KRAS mCRC treated with anti-EGFR MoAbs. BRAF mutation may be used as an additional biomarker for the selection of mCRC patients who might benefit from anti-EGFR MoAbs therapy.

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Acknowledgment

This study was supported by Guangdong Province “211 Project” (Grant No. GW201004).

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Authors and Affiliations

  1. Department of Epidemiology, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou, China

    Chen Mao, Ru-Yan Liao, Xi-Wen Wang & Qing Chen

  2. Department of Medical Oncology, Cancer Hospital, Fudan University, Shanghai, China

    Li-Xin Qiu

  3. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China

    Li-Xin Qiu

  4. Longgang Center for Disease Control and Prevention of Shenzhen, Shenzhen, China

    Hong Ding

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  1. Chen Mao
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  2. Ru-Yan Liao
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  6. Qing Chen
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Correspondence to Qing Chen.

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Mao, C., Liao, RY., Qiu, LX. et al. BRAF V600E mutation and resistance to anti-EGFR monoclonal antibodies in patients with metastatic colorectal cancer: a meta-analysis. Mol Biol Rep 38, 2219–2223 (2011). https://doi.org/10.1007/s11033-010-0351-4

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  • DOI: https://doi.org/10.1007/s11033-010-0351-4

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