title: The role of biological therapy in metastatic colorectal cancer after first-line treatment: a meta-analysis of randomised trials.
abstract: OBJECTIVE
  Biologic agents have achieved variable results in relapsed metastatic colorectal cancer (mCRC). Systematic meta-analysis was undertaken to determine the efficacy of biological therapy.
  
  
  METHODS
  Major databases were searched for randomised studies of mCRC after first-line treatment comparing (1) standard treatment plus biologic agent with standard treatment or (2) standard treatment with biologic agent with the same treatment with different biologic agent(s). Data were extracted on study design, participants, interventions and outcomes. Study quality was assessed using the MERGE criteria. Comparable data were pooled for meta-analysis.
  
  
  RESULTS
  Twenty eligible studies with 8225 patients were identified. The use of any biologic therapy improved overall survival with hazard ratio (HR) 0.87 (95% confidence interval (CI) 0.82-0.91, P<0.00001), progression-free survival (PFS) with HR 0.71 (95% CI 0.67-0.74, P<0.0001) and overall response rate (ORR) with odds ratio (OR) 2.38 (95% CI 2.03-2.78, P<0.00001). Grade 3/4 toxicity was increased with OR 2.34. Considering by subgroups, EGFR inhibitors (EGFR-I) in the second-line setting and anti-angiogenic therapies (both in second-line and third-line and beyond settings) all improved overall survival, PFS and ORR. EGFR-I in third-line settings improved PFS and ORR but not OS.
  
  
  CONCLUSIONS
  The use of biologic agents in mCRC after first-line treatment is associated with improved outcomes but increased toxicity.
authors: St Vincent's Clinical School, University of New South Wales, Sydney, NSW 2052, Australia.
authors: E
authors: E
authors: Segelov
authors: Royal North Shore Hospital, St Leonards, Sydney, NSW 2065, Australia.
authors: D
authors: D
authors: Chan
authors: Monash University and Cabrini Hospital, Melbourne, VIC 3800, Australia.
authors: J
authors: J
authors: Shapiro
authors: The Queen Elizabeth Hospital and University of Adelaide, Woodville South, SA 5011, Australia.
authors: T J
authors: TJ
authors: Price
authors: Flinders University and Flinders Medical Centre, Flinders Centre for Innovation in Cancer, Bedford Park, SA, 5042, Australia.
authors: C S
authors: CS
authors: Karapetis
authors: Austin Health, VIC 3084, Australia.
authors: N C
authors: NC
authors: Tebbutt
authors: Royal North Shore Hospital, St Leonards, Sydney, NSW 2065, Australia.
authors: N
authors: N
authors: Pavlakis
mesh_terms: D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D001691:Biological Therapy / Q000009:adverse effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors
chemical_list: D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D042461:Vascular Endothelial Growth Factor A; D066246:ErbB Receptors; D040262:Receptors, Vascular Endothelial Growth Factor