631 - BRAFV600E mutation analysis in patients with metastatic colorectal cancer (mCRC) in daily clinical practice: correlations with clinical characterist...

Date 28 September 2012
Event ESMO Congress 2012
Session Publication Only
Topics Biomarkers
Colon Cancer
Rectal Cancer
Presenter Zacharenia Saridaki
Authors Z. Saridaki1, M. Tzardi2, M. Sfakianaki3, C. Papadaki3, K. Mpananis3, E. Tsakalaki3, M. Trypaki3, I. Messaritakis3, V. Georgoulias4, J. Souglakos4
  • 1Laboratory Of Tumor Cell Biology, University of Crete, School of Medicine, 71110 - Heraklion/GR
  • 2Laboratory Of Pathology, University of Crete, School of Medicine, 71110 - Heraklion/GR
  • 3Laboratory Of Tumor Cell Biology, School of Medicine, University of Crete, 71110 - Heraklion/GR
  • 4Medical Oncology, University Hospital of Heraklion, 71110 - Heraklion/GR

Abstract

Aim

To evaluate the usefulness of the BRAFV600E detection in the daily clinical practice, it's clinical correlations and prognostic/predictive values in a prospective database of patients with mCRC.

Patients and methods

442 mCRC patients treated with systemic chemotherapy ± biologics at the Medical Oncology Department of the University Hospital of Heraklion from 1-07-07 were prospectively analyzed. The BRAF mutation was assessed by RT-qPCR using the allelic discrimination method. The laboratory findings were correlated with patients' clinical-pathologic characteristics and the treatment outcome.

Results

The median age was 68 years of age (21-89) while 37% of them were > 65 old; 61% were male, in 71% of them the primary tumor was located in the colon and in 29% in the rectum 48% of the tumors were low grade and 21% presented mucinous features. Salvage cetuximab or panitumumab therapy was administered to 228 patients with KRASwt tumors. The BRAF mutation was detected in 32 (7.5%) patients. Statistically significant higher incidence of the BRAF mutation was observed in patients with ECOG-PS 2 (p = 0.0001), > 65 years old (p = 0.001), primaries located in the right colon (p = 0.004), lowgrade tumors (p = 0.001) and in those with mucinous features (p = 0.021). Patients whose tumors harbored the BRAF mutation had a reduced progression-free survival (PFS) (4.1 months) compared with the wild-type (wt) (11.4 months, p < 0.0001). The overall survival (OS) of the patients with BRAF mutation was statistically significantly shorter (13.5 months) compared with the wt ones (33.3 months, p < 0.0001). In the multivariate analysis the BRAF mutation detection emerged as independent factor associated with reduced PFS (HR: 4.1, 95% CI 2.7-6.2, p < 0.0001) and OS (HR: 5.9, 95% CI 3.7-9.5, p < 0.0001). Among the patients treated with anti-EGFR moAbs salvage therapy, the BRAF mutation was correlated with reduced PFS (2.2 vs 6.0 months, p < 0.0001) and OS (4.3 vs 17.4 months, p < 0.0001).

Conclusion

Our results document the unfavorable prognostic value of the BRAFV600E mutation and advocate in favor of its predictive value towards anti-EGFR moAbs therapy.

Disclosure

All authors have declared no conflicts of interest.