RESEARCH ARTICLE
Does the Chemotherapy Backbone Impact on the Efficacy of Targeted Agents in Metastatic Colorectal Cancer? A Systematic Review and Meta-Analysis of the Literature David L. Chan1*, Nick Pavlakis1, Jeremy Shapiro2, Timothy J. Price3, Christos S. Karapetis4, Niall C. Tebbutt5, Eva Segelov6
a11111
1 Royal North Shore Hospital, Northern Clinical School, University of Sydney, St Leonards, New South Wales, Australia, 2 Department of Medical Oncology, Monash University, Victoria, Australia, 3 The Queen Elizabeth Hospital and University of Adelaide, South Australia, Australia, 4 Flinders University and Flinders Medical Centre, Flinders Centre for Innovation in Cancer, Bedford Park, South Australia, Australia, 5 Austin Health, Victoria, Australia, 6 St Vincent’s Clinical School, University of New South Wales, NSW, Australia *
[email protected]
OPEN ACCESS Citation: Chan DL, Pavlakis N, Shapiro J, Price TJ, Karapetis CS, Tebbutt NC, et al. (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 10(8): e0135599. doi:10.1371/ journal.pone.0135599
Abstract Importance The EGFR inhibitors (EGFR-I) cetuximab and panitumumab and the angiogenesis inhibitors (AIs) bevacizumab and aflibercept have demonstrated varying efficacy in mCRC.
Editor: Rafael Rosell, Catalan Institute of Oncology, SPAIN Received: May 1, 2015 Accepted: July 23, 2015 Published: August 14, 2015 Copyright: © 2015 Chan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: All relevant data are within the paper and its Supporting Information files. Funding: The authors have no support or funding to report. Competing Interests: DC has received honoraria from Roche and a travel grant from Sanofi. NP has received honoraria from Bayer, Roche and Sanofi, provided advice to Roche, Merck, Bayer, Sanofi and Amgen, and received a travel grant from Roche. JS has provided advice to Merck, Sanofi and Roche. TP
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.
PLOS ONE | DOI:10.1371/journal.pone.0135599 August 14, 2015
1 / 17
Chemotherapy and Targeted Agents in mCRC
has provided advice to Merck, Amgen, Sanofi and Roche. CK has provided advice to Merck, Amgen and Roche. ES has provided advice to Merck, Amgen, Sanofi and Roche. This does not alter the authors' adherence to all PLOS ONE policies on sharing data and materials.
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, p50% and p
