title: PIK3CA mutation is associated with poor survival among patients with metastatic colorectal cancer following anti-EGFR monoclonal antibody therapy: a meta-analysis.
abstract: OBJECTIVE
  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.
authors: Department of General Surgery, Huashan Hospital, Fudan University, 12 Middle Wulumuqi Road, Shanghai 200040, China.
authors: Shuangjie
authors: S
authors: Wu
authors: Yu
authors: Y
authors: Gan
authors: Xinhai
authors: X
authors: Wang
authors: Jun
authors: J
authors: Liu
authors: Mengjun
authors: M
authors: Li
authors: Yifan
authors: Y
authors: Tang
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics; D058534:Class I Phosphatidylinositol 3-Kinases; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D006801:Humans; D009154:Mutation; D009362:Neoplasm Metastasis; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D017594:Publication Bias; D018631:ras Proteins / Q000235:genetics
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins