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Defective Mismatch Repair and Benefit from Bevacizumab for Colon Cancer: Findings from NSABP C-08

Authors
 Kay Pogue-Geile  ;  Greg Yothers  ;  Yusuke Taniyama  ;  Noriko Tanaka  ;  Patrick Gavin  ;  Linda Colangelo  ;  Nicole Blackmon  ;  Corey Lipchik  ;  Seong Rim Kim  ;  Saima Sharif  ;  Carmen Allegra  ;  Nicholas Petrelli  ;  Michael J. O’Connell  ;  Norman Wolmark  ;  Soonmyung Paik 
Citation
 JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, Vol.105(13) : 989-992, 2013 
Journal Title
 JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE 
ISSN
 0027-8874 
Issue Date
2013
MeSH
Adult ; Aged ; Angiogenesis Inhibitors/administration & dosage ; Angiogenesis Inhibitors/therapeutic use* ; Antibodies, Monoclonal, Humanized/administration & dosage ; Antibodies, Monoclonal, Humanized/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Bevacizumab ; Chemotherapy, Adjuvant ; Colonic Neoplasms/drug therapy* ; Colonic Neoplasms/genetics* ; Colonic Neoplasms/pathology ; DNA Mismatch Repair/drug effects* ; Female ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Neoplasm Staging ; Odds Ratio ; Organoplatinum Compounds/administration & dosage ; Proto-Oncogene Proteins B-raf/genetics ; Treatment Failure ; Vascular Endothelial Growth Factor A/antagonists & inhibitors
Keywords
Adult ; Aged ; Angiogenesis Inhibitors/administration & dosage ; Angiogenesis Inhibitors/therapeutic use* ; Antibodies, Monoclonal, Humanized/administration & dosage ; Antibodies, Monoclonal, Humanized/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Bevacizumab ; Chemotherapy, Adjuvant ; Colonic Neoplasms/drug therapy* ; Colonic Neoplasms/genetics* ; Colonic Neoplasms/pathology ; DNA Mismatch Repair/drug effects* ; Female ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Neoplasm Staging ; Odds Ratio ; Organoplatinum Compounds/administration & dosage ; Proto-Oncogene Proteins B-raf/genetics ; Treatment Failure ; Vascular Endothelial Growth Factor A/antagonists & inhibitors
Abstract
National Surgical Adjuvant Breast and Bowel Project protocol C-08 tested the worth of adding 1 year of bevacizumab to oxaliplatin-based standard adjuvant chemotherapy regimen in the treatment of stage II/III colon cancer. Although the overall result was negative, the possibility that a molecularly defined subset could benefit from bevacizumab cannot be ruled out. We performed post hoc Cox regression analyses to test for marker-by-treatment interactions for standard pathological features and survival analyses using the Kaplan-Meier method. All statistical tests were two-sided and considered statistically significant at the .05 level. Patients diagnosed with mismatch repair defective (dMMR) tumors derived statistically significant survival benefit from the addition of bevacizumab (hazard ratio [HR] = 0.52; 95% confidence interval [CI] = 0.29 to 0.94; P = .02) in contrast with no benefit in patients diagnosed with mismatch repair proficient tumors (HR = 1.03; 95% CI = 0.84 to 1.27; p = .78; P(interaction)= .04). Although a post hoc finding, this data suggests that a molecularly defined subset of colon cancer patients may derive clinical benefit from antiangiogenesis agents and underscores the need for independent validation in other clinical trials.
Full Text
http://jnci.oxfordjournals.org/content/105/13/989.long
DOI
10.1093/jnci/djt140
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
Yonsei Authors
Paik, Soon Myung(백순명) ORCID logo https://orcid.org/0000-0001-9688-6480
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/89034
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