The role of biological therapy in metastatic colorectal cancer after first-line treatment: a meta-analysis of randomised trials

Br J Cancer. 2014 Sep 9;111(6):1122-31. doi: 10.1038/bjc.2014.404. Epub 2014 Jul 29.

Abstract

Purpose: 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.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Angiogenesis Inhibitors / adverse effects
  • Angiogenesis Inhibitors / therapeutic use*
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / therapeutic use*
  • Biological Therapy* / adverse effects
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / pathology*
  • Disease-Free Survival
  • ErbB Receptors / antagonists & inhibitors*
  • Humans
  • Randomized Controlled Trials as Topic
  • Receptors, Vascular Endothelial Growth Factor / antagonists & inhibitors
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors

Substances

  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal
  • Vascular Endothelial Growth Factor A
  • ErbB Receptors
  • Receptors, Vascular Endothelial Growth Factor