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
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.
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.Additional details
- Eprint ID
- 24146
- Resolver ID
- CaltechAUTHORS:20110621-091835589
- Valley Foundation
- Created
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2011-06-29Created from EPrint's datestamp field
- Updated
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2021-11-09Created from EPrint's last_modified field