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

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 6.4 months in the hENT1low compared to 6.9 months 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 5.7 months in the hENT1low compared to 4.4 months 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 7.5 months and hENT1high patients an overall survival of 4.4 months (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.