630 - Potential biomarkers for response to cetuximab in patients with metastatic colorectal cancer (mCRC). A Hellenic Cooperative Oncology Group study

Date 28 September 2012
Event ESMO Congress 2012
Session Publication Only
Topics Colon Cancer
Rectal Cancer
Translational Research
Presenter Evangelia Razis
Authors E. Razis1, M. Bobos1, W. De Roock2, M. Bai1, A. Gousia1, I. Xanthakis1, E. Tsolaki1, P. Papakostas1, S. Tejpar3, G. Fountzilas4
  • 1Data Office, Hellenic Cooperative Oncology Group (HeCOG), Athens/GR
  • 2Human Genetics, Katholieke Universiteit Leuven, Leuven/BE
  • 3Digestive Oncology Unit, University Hospital Gasthuisberg, BE-3000 - Leuven/BE
  • 4Medical Oncology Clinic, Hellenic Cooperative Oncology Group (HeCOG), Athens/GR

Abstract

Background

Cetuximab has improved outcome of patients (pts) with mCRC. KRAS has emerged as a marker of resistance to monoclonal antibodies against EGFR, including cetuximab. Further biomarkers for response to cetuximab are being explored.

Methods

In a heterogeneous cetuximab-treated population we retrospectively evaluated formalin-fixed paraffin-embedded tissue for EGFR and PTEN by Fluorescence In Situ Hybridization (FISH) and for PIK3CA and KRAS mutations by PCR and examined the association of these markers with patient outcome.

Results

Two hundred twenty-three cetuximab-treated mCRC pts were identified, of which 38 were treated in first line, 107 in second and 78 in ≥ 3rd line. Cetuximab was used with irinotecan-based therapy in 54.3% and with oxaliplatin in 26.9% of the cases. Two pts achieved a complete response, 53 a partial response and 65 stable disease for a clinical benefit rate of 63.2%. EGFR amplification was noted in 5 cases, PTEN deletion in 58 and PTEN gain in 2. Finally, KRAS was mutated in 72 cases, and PIK3CA in 37. The mutations detected for KRAS were G12 (45 pts, 62.5%), G13 (16 pts, 22.2%), G61 (4 pts, 5.6%) and A146 (7 pts, 9.7%) and for PIK3CA Exon9 (20 pts, 54.1%), Exon20 (5 pts, 13.5%) and other (12 pts, 32.4%). No associations were found between these markers. PTEN deletion was associated with a higher overall response rate (ORR) (p = 0.031), while the other markers were not. Progression-free survival (PFS) and survival were calculated from initiation of cetuximab. PFS was numerically associated with EGFR gain but the numbers (5 gain vs. 138 normal) do not allow for a sound result. Additionally, given the different impact of diverse KRAS mutations on outcome, we evaluated the outcome in relation to the G12 mutations. The latter exhibited a trend for decreased survival (p = 0.057).

Conclusions

After a median follow up of 55.3 months (5.8-88.4 months), PTEN deletion was associated with improved ORR to cetuximab. Further examination of EGFR and PTEN by immunohistochemistry is in progress.

Disclosure

E. Razis: Dr E. Razis received research grant from Merck S.A. and Roche (Hellas) S.A.

All other authors have declared no conflicts of interest.