TY - JOUR
T1 - Mismatch repair status and BRAF mutation status in metastatic colorectal cancer patients: a pooled analysis of the CAIRO, CAIRO2, COIN, and FOCUS studies
AU - Venderbosch, Sabine
AU - Nagtegaal, Iris D.
AU - Maughan, Tim S.
AU - Smith, Christopher G.
AU - Cheadle, Jeremy P.
AU - Fisher, David
AU - Kaplan, Richard
AU - Quirke, Philip
AU - Seymour, Matthew T.
AU - Richman, Susan D.
AU - Meijer, Gerrit A.
AU - Ylstra, Bauke
AU - Heideman, Danielle A. M.
AU - de Haan, Anton F. J.
AU - Punt, Cornelis J. A.
AU - Koopman, Miriam
PY - 2014
Y1 - 2014
N2 - To determine the prevalence and prognostic value of mismatch repair (MMR) status and its relation to BRAF mutation (BRAF(MT)) status in metastatic colorectal cancer (mCRC). 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. The primary tumors of 3,063 patients were analyzed, of which 153 (5.0%) exhibited deficient MMR (dMMR) and 250 (8.2%) a BRAF(MT). BRAF(MT) 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 BRAF(MT) compared with BRAF wild-type (BRAF(WT)) 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 BRAF(MT) within the group of patients with pMMR, but not for BRAF status within dMMR, or MMR status within BRAF(WT) or BRAF(MT). Prevalence of dMMR and BRAF(MT) 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 BRAF(MT) status
AB - To determine the prevalence and prognostic value of mismatch repair (MMR) status and its relation to BRAF mutation (BRAF(MT)) status in metastatic colorectal cancer (mCRC). 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. The primary tumors of 3,063 patients were analyzed, of which 153 (5.0%) exhibited deficient MMR (dMMR) and 250 (8.2%) a BRAF(MT). BRAF(MT) 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 BRAF(MT) compared with BRAF wild-type (BRAF(WT)) 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 BRAF(MT) within the group of patients with pMMR, but not for BRAF status within dMMR, or MMR status within BRAF(WT) or BRAF(MT). Prevalence of dMMR and BRAF(MT) 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 BRAF(MT) status
U2 - https://doi.org/10.1158/1078-0432.CCR-14-0332
DO - https://doi.org/10.1158/1078-0432.CCR-14-0332
M3 - Article
C2 - 25139339
SN - 1078-0432
VL - 20
SP - 5322
EP - 5330
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 20
ER -