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Effect of KRAS Mutational Status in Advanced Colorectal Cancer on the Outcomes of Anti-Epidermal Growth Factor Receptor Monoclonal Antibody Therapy: A Systematic Review and Meta-analysis

Lin, Albert Y. and Buckley, Nicholas S. and Lu, An-Ting T. and Kouzminova, Natalia B. and Salpeter, Shelley R. (2011) Effect of KRAS Mutational Status in Advanced Colorectal Cancer on the Outcomes of Anti-Epidermal Growth Factor Receptor Monoclonal Antibody Therapy: A Systematic Review and Meta-analysis. Clinical Colorectal Cancer, 10 (1). pp. 63-69. ISSN 1533-0028. https://resolver.caltech.edu/CaltechAUTHORS:20110621-091835589

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Abstract

Background: Emerging data suggest that somatic KRAS mutation in advanced colorectal cancer is a strong predictor of non-response to anti-epidermal growth factor receptor antibody (anti-EGFR) therapy. Patients and Methods: A comprehensive search through March 2010 identified randomized controlled trials in metastatic colorectal cancer that evaluated chemotherapy regimens or best supportive care, with and without anti-EGFR therapy. Outcomes included progression-free survival (PFS), median overall survival (OS), and predictive test performance. Results: In pooled data from 8 trials with 5325 patients, the addition of anti-EGFR to standard chemotherapy resulted in improved PFS (HR 0.66 [95% CI, 0.53-0.82]) in patients with wild-type KRAS in the tumor tissue, but not in patients with KRAS mutation (HR 1.07 [95% CI, 0.91-1.27]). Anti-EGFR treatment in the wild-type group did not significantly improve median OS. As a predictive biomarker, KRAS mutation had a positive likelihood ratio of 2.0 (95% CI, 1.45-2.76) in predicting nonresponse to anti-EGFR treatment. Conclusion: In patients with advanced colorectal cancer, the addition of anti-EGFR treatment to standard chemotherapy improves PFS for those with wild-type, but not mutant KRAS status. KRAS gene mutation testing provides a fair biomarker in predicting non-response to anti-EGFR treatment.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.3816/CCC.2011.n.009DOIUNSPECIFIED
http://cigjournals.metapress.com/content/x0gn66qu67lx3767/?p=7b577d4e784948e9be0e3d2bf9640649&pi=9PublisherUNSPECIFIED
Additional Information:© 2011 Elsevier Inc. Submitted: Jan 28, 2010; Revised: Jun 17, 2010; Accepted: Jun 29, 2010. This work is supported, in part, by The Valley Foundation.
Funders:
Funding AgencyGrant Number
Valley Foundation UNSPECIFIED
Subject Keywords:Anti-EGFR treatment, Panitumumab
Issue or Number:1
Record Number:CaltechAUTHORS:20110621-091835589
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20110621-091835589
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:24146
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:29 Jun 2011 21:29
Last Modified:03 Oct 2019 02:53

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