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PIK3CA mutation is associated with poor survival among patients with metastatic colorectal cancer following anti-EGFR monoclonal antibody therapy: a meta-analysis

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Abstract

Purpose

PIK3CA mutation appears to predict a lack of response to anti-EGFR monoclonal antibody (mAb) treatment in patients with metastatic colorectal cancer (mCRC). However, the predictive value of PIK3CA mutations for survival remains inconclusive. Here, we pooled the data from published studies to estimate the association between PIK3CA mutation and survival outcomes in mCRC patients treated with anti-EGFR mAbs.

Methods

Studies investigating the association of PIK3CA mutations with clinical survival outcomes of mCRC patients treated with anti-EGFR mAbs were systematically identified. The overall hazard ratio (HR) was estimated by using fixed effect model or random effect model according to heterogeneity between trails.

Results

Eight studies that reported survival outcome in 839 mCRC patients were included. In unselected patients, we found that PIK3CA mutations were significantly associated with poorer PFS [8 studies, 839 patients; HR = 1.53; 95 % confidence interval (CI) 1.28–1.84; P < 0.001] and OS (5 studies; 587 patients; HR = 1.28; 95 % CI 1.05–1.56; P = 0.015). With increased predictive power in KRAS wild-type patients (3 studies; 275 patients), the overall HR for PFS was 2.44 (95 % CI 1.33–4.48; P = 0.004) and was statistically significant. We also observed a worse OS in KRAS wild-type patients with PIK3CA mutations (2 studies; 163 patients; HR = 1.37; 95 % CI 0.80–2.35; P = 0.258), although the result was not statistically significant due to small sample size.

Conclusions

PIK3CA mutation is a promising predictive biomarker for poor survival in mCRC patients treated with anti-EGFR mAbs, particularly in KRAS wild-type patients.

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Acknowledgments

This study was supported by Research Fund of Shanghai Municipal Health Bureau (Grant No. 2009011). We appreciate Dr. Xianjing Zhang for her help in statistic analysis, and Dr. Xiaoming Hu for her excellent editorial assistance.

Conflict of interest

We declare that we have no conflict of interest.

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Authors and Affiliations

  1. Department of General Surgery, Huashan Hospital, Fudan University, 12 Middle Wulumuqi Road, Shanghai, 200040, China

    Shuangjie Wu, Xinhai Wang, Jun Liu, Mengjun Li & Yifan Tang

  2. State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, 25/Ln. 2200 Xietu Road, Shanghai, 200032, China

    Yu Gan

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  1. Shuangjie Wu
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  2. Yu Gan
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  3. Xinhai Wang
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  6. Yifan Tang
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Corresponding author

Correspondence to Yifan Tang.

Additional information

S. Wu and Y. Gan contributed equally to this work.

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Wu, S., Gan, Y., Wang, X. et al. PIK3CA mutation is associated with poor survival among patients with metastatic colorectal cancer following anti-EGFR monoclonal antibody therapy: a meta-analysis. J Cancer Res Clin Oncol 139, 891–900 (2013). https://doi.org/10.1007/s00432-013-1400-x

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