521O - Deficient mismatch repair (DMMR) and BRAF mutation (MT) status in patients (pts) with metastatic colorectal cancer (mCRC): a meta-analysis of the CA...

Date 01 October 2012
Event ESMO Congress 2012
Session Gastrointestinal tumors, colorectal
Topics Anti-Cancer Agents & Biologic Therapy
Biomarkers
Colon Cancer
Rectal Cancer
Presenter Cornelis J.A. Punt
Authors S. Venderbosch1, T. De Haan2, D.A.M. Heideman3, T.S. Maughan4, C.G. Smith5, P. Quirke6, S.D. Richman6, I.D. Nagtegaal1, C.J.A. Punt7, M. Koopman8
  • 1Pathology, Radboud University Nijmegen Medical Centre, 6500HB - Nijmegen/NL
  • 2Epidemiology, Biostatistics And Health Technology Assessment, Radboud University Nijmegen Medical Centre, Nijmegen/NL
  • 3Department Of Pathology, VU University Medical Centre, Amsterdam/NL
  • 4Oncology, Gray Institute for Radiation Oncology & Biology University of Oxford, Oxford/UK
  • 5School Of Medicine, Cardiff University, Cardiff/UK
  • 6Pathology And Tumour Biology, Leeds Institute of Molecular Medicine, Leeds/UK
  • 7Department Of Medical Oncology, Academic Medical Center, Amsterdam/NL
  • 8Medical Oncology, University Hospital Utrecht, NL-3508 GA - Utrecht/NL

Abstract

Introduction

In stage II-III CRC the overall incidence of BRAF mt and dMMR is 8% and 10-20%, resp. The incidence of BRAF mt in sporadic dMMR is high (24%, Roth et al., JCO 2010), and BRAF mt, in contrast to dMMR, has a negative prognostic value. The incidence of dMMR and BRAF mt in mCRC is approx. 4% and 8%, resp. No data from large series of mCRC pts are available on the prognostic value of BRAF mt in combination with dMMR.

Methods

We performed a meta-analysis of 4 mCRC trials: CAIRO, CAIRO2, COIN and FOCUS. The primary outcome measure was the hazard ratio (HR) for progression free survival (PFS) and overall survival (OS) in relation to BRAF and MMR status. For the meta-analysis a cox regression analysis was performed on individual pt data.

Results

In total 3064 pts were analysed, of whom 151 (4.9%) exhibited dMMR, and 263 (8.6%) BRAF mt. A BRAF mt was observed in 211 (7.2%), and 52 (34.4%) of the pts with a proficient mismatch repair system (pMMR) and dMMR, resp. PFS was significantly worse for dMMR vs. pMMR pts (HR 1.22; 95% CI, 1.03-1.46), but not OS (HR 1.13; 95% CI, 0.94-1.36). PFS and OS were significantly worse for BRAF mt vs. BRAF wildtype (wt) pts (HR 1.28; 95% CI, 1.12-1.46 and HR 1.81; 95% CI, 1.57-2.09, resp.). Within the pMMR group, BRAF mt pts had a significantly worse PFS and OS compared to BRAF wt pts (HR 1.32; 95% CI 1.09-1.61, and HR 1.88; 95% CI 1.53-2.30, resp.). Within the dMMR group no significant differences were found for PFS and OS in BRAF mt pts vs. BRAF wt pts (HR 1.05; 95% CI 0.65-1.68, and HR 1.49; 95% CI 0.91-2.43, resp.). Within the BRAF mt group PFS and OS were not significantly different between pMMR and dMMR pts (HR 0.96; 95% CI 0.63-1.47, and HR 1.03; 95% CI 0.67-1.59, resp.). Within the BRAF wt group, PFS and OS were not significantly different for pMMR vs. dMMR pts (HR 1.32; 95% CI 0.99-1.75, and HR 1.22; 95% CI 0.90-1.65, resp.).

Conclusion

In this meta-analysis of mCRC pts we observed a higher incidence of BRAF mt in dMMR than reported for early-stage CRC pts. In mCRC pts, dMMR is associated with a worse PFS compared to pMMR. The prognostic role of BRAF mt in mCRC is restricted to pMMR pts. Our data confirm the worse prognostic value of BRAF mt vs BRAF wt.

Disclosure

All authors have declared no conflicts of interest.