641 - Prognostic value of BRAF and KRAS mutations in colorectal cancer patients

Date 28 September 2012
Event ESMO Congress 2012
Session Publication Only
Topics Biomarkers
Colon Cancer
Rectal Cancer
Presenter Eleonor Murata
Authors E.P. Murata1, A. Stradella1, D. Páez1, M. Tobeña Puyal1, A. Sebio Garcia1, A. Gonzalez1, E. Targarona1, M. Baiget2, A. Barnadas1, M. Martín-Richard1
  • 1Medical Oncology, Hospital de la Santa Creu i Sant Pau, 08025 - Barcelona/ES
  • 2Deparment Of Genetics, Hospital de la Santa Creu i Sant Pau, 08041 - Barcelona/ES

Abstract

Background

KRAS mutation has been established as a predictive marker of resistance to antiEGFR therapy in patients (pts) with colorectal cancer (CRC) but the role of BRAF is not yet clear. Both gene mutations have also been studied as prognostic factors but results are contradictory. AntiEGFR therapies impair evaluation of KRAS and BRAF as prognostic factors when overall survival is an endpoint. We hypothesized that if KRAS or BRAF were prognostic factors, they would influence time to relapse (TTR) after complete tumor resection.

Methods

Patients who underwent surgery between 2007 and 2011 for stage II and III CRC were retrieved from our database. Codon 12 and 13 KRAS mutations and V600E BRAF mutation were analyzed. Clinical characteristics and mutation status were correlated with TTR.

Results

We analyzed 170 pts with a median age of 66 (26 – 86) years. Tumors were located in the right colon in 27% of pts, in the transverse colon in 3%, in the left colon in 41%, and in the rectum in 29%. Most (55.3%) were stage III; 59% received adjuvant chemotherapy. KRAS and BRAF mutations were present in 66 (38.8%) and 5 (2.9%) pts respectively, and both were mutually exclusive. The most frequent KRAS mutations were: G12D (39.3%), G12V (27.2%), G13D (15.1%). Median TTR was 71 weeks (w) (13 – 520w). V600E BRAF mutation was the only factor associated with TTR. TTR was 42 w in tumors with the BRAF mutation and 74 w in wild-type tumors (p = 0.041). Among KRAS mutations, KRAS G12V conferred a significantly longer TTR (100w) than the other subtype mutations (69 w; p = 0.05).

Conclusions

Our results suggest that V600E BRAF mutation is a negative prognostic factor in CRC, conferring a shorter time to relapse. Additionally, the KRAS G12V determines a different behavior among KRAS mutation tumors.

Disclosure

All authors have declared no conflicts of interest.