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Mismatch repair status and BRAF mutation status in metastatic colorectal cancer patients: a pooled analysis of the CAIRO, CAIRO2, COIN, and FOCUS studies

Venderbosch, S., Nagtegaal, I. D., Maughan, Timothy Stanley, Smith, C. G., Cheadle, Jeremy Peter, Fisher, D., Kaplan, R., Quirke, P., Seymour, M. T., Richman, S. D., Meijer, G. A., Ylstra, B., Heideman, D. A. M., de Haan, A. F. J., Punt, C. J. A. and Koopman, M. 2014. Mismatch repair status and BRAF mutation status in metastatic colorectal cancer patients: a pooled analysis of the CAIRO, CAIRO2, COIN, and FOCUS studies. Clinical Cancer Research 20 (20) , pp. 5322-5330. 10.1158/1078-0432.CCR-14-0332

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Abstract

Purpose: To determine the prevalence and prognostic value of mismatch repair (MMR) status and its relation to BRAF mutation (BRAFMT) status in metastatic colorectal cancer (mCRC). Experimental Design: A pooled analysis of four phase III studies in first-line treatment of mCRC (CAIRO, CAIRO2, COIN, and FOCUS) was performed. Primary outcome parameter was the hazard ratio (HR) for median progression-free survival (PFS) and overall survival (OS) in relation to MMR and BRAF. For the pooled analysis, Cox regression analysis was performed on individual patient data. Results: The primary tumors of 3,063 patients were analyzed, of which 153 (5.0%) exhibited deficient MMR (dMMR) and 250 (8.2%) a BRAFMT. BRAFMT was observed in 53 (34.6%) of patients with dMMR tumors compared with 197 (6.8%) of patients with proficient MMR (pMMR) tumors (P < 0.001). In the pooled dataset, median PFS and OS were significantly worse for patients with dMMR compared with pMMR tumors [HR, 1.33; 95% confidence interval (CI), 1.12–1.57 and HR, 1.35; 95% CI, 1.13–1.61, respectively), and for patients with BRAFMT compared with BRAF wild-type (BRAFWT) tumors (HR, 1.34; 95% CI, 1.17–1.54 and HR, 1.91; 95% CI, 1.66–2.19, respectively). PFS and OS were significantly decreased for patients with BRAFMT within the group of patients with pMMR, but not for BRAF status within dMMR, or MMR status within BRAFWT or BRAFMT. Conclusions: Prevalence of dMMR and BRAFMT in patients with mCRC is low and both biomarkers confer an inferior prognosis. Our data suggest that the poor prognosis of dMMR is driven by the BRAFMT status.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Medicine
Subjects: R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Publisher: American Association for Cancer Research
ISSN: 1078-0432
Date of First Compliant Deposit: 30 March 2016
Last Modified: 27 Jun 2019 21:53
URI: http://orca-mwe.cf.ac.uk/id/eprint/74684

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