EGFR gene copy number, KRAS and BRAF status, PTEN and AKT expression analysis in patients with metastatic colon cancer treated with anti-EGFR monoclonal antibodies ± chemotherapy

Abstract

e15055 Background: Cetuximab and panitumumab have proven to be effective in metastatic colon cancer (mCRC). KRAS mutation has been demonstrated to be a biomarker of resistance to both monoclonal antibodies. However the status and expression of other biomarkers of the RAS-RAF-MAPK signalling pathway can have a crucial role in sensitivity to anti-EGFR monoclonal antibodies. Methods: We have retrospectively analyzed tumor tissue biomarkers including EGFR gene copy number (GCN) by FISH, KRAS and BRAF status by PCR-based sequencing, PTEN and AKT expression by IHC in patients with mCRC treated with cetuximab and panitumumab ±chemotherapy. Response to treatment, TTP and OS were evaluated. Results: Sixty-three patients (pts) have been analyzed. Median age was 59 years (34–80); 53 pts had received cetuximab and 10 pts panitunumab. Concomitatnt chemotherapy was FOLFIRI, CPT-11, FOLFOX4 and Xeliri in 35, 13, 6 and 4 pts respectively. Five pts had received monoclonal antibodies only. Twenty- one pts were treated in 1st-2nd line and 42 pts in 3rd-4th line. So far EGFR GCN is available on 55 pts, KRAS and BRAF on 63 pts, PTEN in primary tumor (PT) on 36 pts and in metastatic (MTS) site on 24 pts, AKT on 19 pts. EGFR/nuclei ratio was > 2.9 in 31 % of the pts, KRAS and BRAF were mutated in 36.5 % and 3 % of the pts respectively; PTEN was positive in 42 % and 79 % in PT and MTS respectively. Moreover 21.8 % of the pts had EGFR/nuclei > 2.9 and CEP7 Polisomy > 50 %. Four pts achieved a partial remission (6.3 %). Partial response rate was 17 % vs. 2.6 % in pts with high and low EGFR GCN respectively (p: 0.007) and 13 % vs. 2.5 % in pts with WT and mutated KRAS respectively (p: 0.048). Median TTP was 3 months (0.83–32.9). It was 4.2 vs. 2.3 mos in pts with WT and mutated KRAS respectively (p: 0.001). Median OS was 9.7 mos (2.03–49.0) and no statistically significant differences were observed according to the biomarkers status. However a trend was observed for pts with KRAS WT 10.6 vs. 7.8 mos and for PTEN positive in PT: 9.0 vs. 5.67 mos. Conclusions: Our data confirm the predictive role of EGFR gene copy number and KRAS status on the response and survival. Complete biomarker characterization is ongoing and an analysis for interaction will be performed. No significant financial relationships to disclose.