Phosphorylated Akt and MAPK expression in primary tumors and in corresponding metastases and clinical outcome in colorectal cancer patients receiving irinotecan-cetuximab.

Abstract

e14086 Background: Other than the well-known EGFR pathway activation via the Ras-Raf-MAP-kinase, a possible role of other potential biomarkers could be relevant in determining resistance to anti-EGFR treatment, such as the protein-serine/threonine kinase Akt. We tried to assess the role of Akt and MAPK expression in metastatic colorectal cancer patients and their relationship with outcome for patients receiving Irinotecan-Cetuximab. Methods: Eligible patients were metastatic colorectal cancer patients treated in 2nd or 3rd line setting with a irinotecan-cetuximab based regimen. Patients were tested for K-ras status and subsequently assessed by immunoistochemistry for pAkt and MAPK expression, both in primary tumours and metastases whenever sufficient tissue was available. The role of pAkt and MAPK expression was evaluated for K-ras wild type patients for different likelihood of response, overall survival and progression free survival. Response was evaluated by RECIST criteria. Survival analysis was performed via Kaplan-Meier method. Results: In metastases pAkt correlated with RR (9% vs. 58%, p=0.004), PFS (2.3 months vs.9.2 months p < 0.0001) and OS (6.1 months vs.26.7 months p < 0.0001) and pMAPK correlated with RR (10% vs, 47%, p = 0.002), PFS (2.3 months vs.8.6 months p < 0.0001) and OS (7.8 months vs.26 months p=0.0004). At multivariate analysis pAkt and pMAPK in metastases were able to independently predict PFS. pAkt in metastases independently correlated with RR as well. Conclusions: pAkt and pMAPK expression in metastases may modulate the activity of EGFR-targeted antibodies. We could speculate that in patients with pAkt and pMAPK metastases expression targeting these factors may be crucial.