Human equilibrative nucleoside transporter 1 is not predictive for gemcitabine efficacy in advanced pancreatic cancer: Translational results from the AIO-PK0104 phase III study with the clone SP120 rabbit antibody

Abstract

BackgroundThe role of human equilibrative nucleoside transporter 1 (hENT1) as a predictive biomarker for gemcitabine efficacy in advanced pancreatic cancer remains unclear to date. Patients and methodsAIO-PK0104 was a German multicenter phase III trial comparing gemcitabine/erlotinib followed by capecitabine (GEC) with capecitabine/erlotinib followed by gemcitabine (CEG) in advanced pancreatic cancer. Archival tumour tissue from 169 of the 274 eligible study patients was available for a central and standardised immunohistochemistry staining for hENT1 expression using the SP120 rabbit monoclonal anti-hENT1 antibody. Within a retrospective translational subgroup analysis, biomarker data were correlated with efficacy end-points. ResultsThirty-nine out of 130 fresh-cut slides were scored as hENT1high (30%), whereas 91 samples were classified as hENT1low (70%). For the 62 patients randomised to CEG median overall survival was estimated with 6.4months in the hENT1low compared to 6.9months in the hENT1high subgroup (Hazard Ratio (HR) 0.88, 95% confidence interval (CI) 0.48–1.61, p=0.67). For the 68 patients randomised to GEC survival was 5.7months in the hENT1low compared to 4.4months in the hENT1high subgroup (HR 1.16, 95% CI 0.69–1.96, p=0.57). In 101 patients receiving gemcitabine at any time during study treatment (either within the 1st- or 2nd-line setting) hENT1low cases had a median overall survival of 7.5months and hENT1high patients an overall survival of 4.4months (HR 1.30, 95% CI 0.84–2.03, p=0.24), respectively. ConclusionWithin this subgroup analysis from Arbeitsgemeinschaft Internistische Onkologie-pancreatic cancer (AIO-PK0104), no evidence supporting the use of hENT1 as a predictive biomarker for gemcitabine efficacy in patients with advanced pancreatic cancer was found.