title: On-treatment markers as predictors to guide anti-EGFR MoAb treatment in metastatic colorectal cancer: a systematic review with meta-analysis.
abstract: OBJECTIVE
  Skin toxicity (ST) and early tumor shrinkage (ETS) are early phenomenon during the anti-epidermal growth factor receptor (EGFR) monoclonal antibody (MoAb) treatment. We conducted a meta-analysis and included relevant studies that reported the impact of ST and ETS on survival- and life quality-based outcome of metastatic colorectal cancer (mCRC) patients treated with anti-EGFR MoAb.
  
  
  METHODS
  Relevant studies were identified from PubMed and Embase reporting the correlation of ST and ETS with the clinical outcome of mCRC patients treated with anti-EGFR MoAb. We also collected evidences on the impact of ST and ETS on absolute benefit acquired from additional anti-EGFR treatment and quality of life (ST only). Pooled hazard ratio and rate difference were all estimated by using random-effects model.
  
  
  RESULTS
  Pooled data revealed that the occurrence of ST and ETS ≥20% (v < 20%) during anti-EGFR MoAb treatment were both associated with better OS, PFS and ORR. This association could not be disturbed by KRAS status. Mean changes in safety follow-up life health state from baseline appeared unaffected by ST. Only mCRC patients with wild-type KRAS tumor who suffered grade 2+ ST could benefit from additional anti-EGFR treatment to chemotherapy or best supportive care (BSC) alone. ETS was also a predictor for absolute survival benefit acquired from additional anti-EGFR treatment for patients with wild-type KRAS tumors, and the more early shrinkage the tumor was, the much benefit was observed.
  
  
  CONCLUSIONS
  ST and ETS are predictive of absolute benefit acquired from anti-EGFR treatment in mCRC patients with wild-type KRAS tumors. These two on-treatment markers can be used for clinical decision-making if no adequate biological markers from tissues are provided.
authors.affiliation: Comprehensive Cancer Center, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Traditional Chinese Medicine, Nanjing, China.|Comprehensive Cancer Center of Drum Tower Hospital, Medical School of Nanjing University, Clinical Cancer Institute of Nanjing University, No. 321 Zhongshan Road, Nanjing, 210008, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Hu
authors.affiliation: Comprehensive Cancer Center, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Traditional Chinese Medicine, Nanjing, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: College of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Zheng
authors.affiliation: Comprehensive Cancer Center of Drum Tower Hospital, Medical School of Nanjing University, Clinical Cancer Institute of Nanjing University, No. 321 Zhongshan Road, Nanjing, 210008, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Cheng
authors.affiliation: Comprehensive Cancer Center of Drum Tower Hospital, Medical School of Nanjing University, Clinical Cancer Institute of Nanjing University, No. 321 Zhongshan Road, Nanjing, 210008, China.
authors.forename: Mi
authors.initials: M
authors.lastname: Yang
authors.affiliation: Comprehensive Cancer Center, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Traditional Chinese Medicine, Nanjing, China.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: Comprehensive Cancer Center of Drum Tower Hospital, Medical School of Nanjing University, Clinical Cancer Institute of Nanjing University, No. 321 Zhongshan Road, Nanjing, 210008, China.
authors.forename: Baorui
authors.initials: B
authors.lastname: Liu
authors.affiliation: Comprehensive Cancer Center, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Traditional Chinese Medicine, Nanjing, China. xiaopingqian@nju.edu.cn.|Comprehensive Cancer Center of Drum Tower Hospital, Medical School of Nanjing University, Clinical Cancer Institute of Nanjing University, No. 321 Zhongshan Road, Nanjing, 210008, China. xiaopingqian@nju.edu.cn.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Qian
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D015415:Biomarkers; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D006801:Humans; D009362:Neoplasm Metastasis; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D012867:Skin / Q000187:drug effects
chemical_list: D000911:Antibodies, Monoclonal; D015415:Biomarkers; C117307:KRAS protein, human; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras)
keywords: Cetuximab; Colorectal cancer; Early tumor shrinkage; On-treatment markers; Panitumumab; Skin toxicity