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Does the Chemotherapy Backbone Impact on the Efficacy of Targeted Agents in Metastatic Colorectal Cancer? A Systematic Review and Meta-Analysis of the Literature

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  • David L Chan
  • Nick Pavlakis
  • Jeremy Shapiro
  • Timothy J Price
  • Christos S Karapetis
  • Niall C Tebbutt
  • Eva Segelov

Abstract

Importance: The EGFR inhibitors (EGFR-I) cetuximab and panitumumab and the angiogenesis inhibitors (AIs) bevacizumab and aflibercept have demonstrated varying efficacy in mCRC. Objective: To document the overall impact of specific chemotherapy regimens on the efficacy of targeted agents in treating patients with mCRC. Data sources: MEDLINE, EMBASE and Cochrane databases were searched to 2014, supplemented by hand-searching ASCO/ESMO conference abstracts. Study Selection: Published RCTs of patients with histologically confirmed mCRC were included if they investigated either 1) chemotherapy with or without a biological agent or 2) different chemotherapy regimens with the same biological agent. EGFR-I trials were restricted to KRAS exon 2 wild-type (WT) populations. Data Extraction and Synthesis: Data were independently abstracted by two authors and trial quality assessed according to Cochrane criteria. The primary outcome was overall survival with secondary endpoints progression free survival (PFS), overall response rate (ORR) and toxicity. Results: EGFR-I added to irinotecan-based chemotherapy modestly improved OS with HR 0.90 (95% CI 0.81–1.00, p = 0.04), but more so PFS with HR 0.77 (95% CI 0.69–0.86, p

Suggested Citation

  • David L Chan & Nick Pavlakis & Jeremy Shapiro & Timothy J Price & Christos S Karapetis & Niall C Tebbutt & Eva Segelov, 2015. "Does the Chemotherapy Backbone Impact on the Efficacy of Targeted Agents in Metastatic Colorectal Cancer? A Systematic Review and Meta-Analysis of the Literature," PLOS ONE, Public Library of Science, vol. 10(8), pages 1-17, August.
    • Handle: RePEc:plo:pone00:0135599
    DOI: 10.1371/journal.pone.0135599
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    References listed on IDEAS

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    1. Si-wei Zhou & Yuan-yuan Huang & Ying Wei & Zhi-min Jiang & Yuan-dong Zhang & Qiong Yang & De-rong Xie, 2012. "No Survival Benefit from Adding Cetuximab or Panitumumab to Oxaliplatin-Based Chemotherapy in the First-Line Treatment of Metastatic Colorectal Cancer in KRAS Wild Type Patients: A Meta-Analysis," PLOS ONE, Public Library of Science, vol. 7(11), pages 1-9, November.
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