Background: The role of pERK, pAKT and p53 as biomarkers in patients with advanced pancreatic cancer has not\nyet been defined.\nMethods: Within the phase III study AIO-PK0104 281 patients with advanced pancreatic cancer received an\nerlotinib-based 1st-line regimen. Archival tissue from 153 patients was available for central immunohistochemistry\nstaining for pERK, pAKT and p53. Within a subgroup analysis, biomarker data were correlated with efficacy endpoints\nand skin rash using a Cox regression model.\nResults: Fifty-five out of 153 patients were classified as pERKlow and 98 patients as pERKhigh; median overall survival\n(OS) was 6.2 months and 5.7 months, respectively (HR 1.29, p = 0.16). When analysing pERK as continuous variable,\nthe pERK score was significantly associated with OS (HR 1.06, 95% CI 1.0-1.12, p = 0.05). Twenty-one of 35 patients\nwere pAKTlow and 14/35 pAKThigh with a corresponding median OS of 6.4 months and 6.8 months, respectively\n(HR 1.03, p = 0.93). Four out of 50 patients had a complete loss of p53 expression, 20 patients a regular expression\nand 26 patients had tumors with p53 overexpression. The p53 status had no impact on OS (p = 0.91); however, a\nsignificant improvement in progression-free survival (PFS) (6.0 vs 1.8 months, HR 0.24, p = 0.02) and a higher rate of\nskin rash (84% vs 25%, p = 0.02) was observed for patients with a regular p53 expression compared to patients with\na complete loss of p53.\nConclusion: pERK expression may have an impact on OS in erlotinib-treated patients with advanced pancreatic\ncancer; p53 should be further investigated for its potential role as a predictive marker for PFS and skin rash.\nTrial registration: NCT00440167 (registration date: February 22, 2007).
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