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 |
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| Institution: | 1. Department of Pathology, Ludwig-Maximilians-University of Munich, Germany;2. Department of Internal Medicine III and Comprehensive Cancer Center, Klinikum Grosshadern, Ludwig-Maximilians-University of Munich, Germany;3. German Cancer Consortium (DKTK), Heidelberg, Germany;4. German Cancer Research Center (DKFZ), Heidelberg, Germany;5. Clovis Oncology Inc., San Francisco, CA, USA;6. Institute of Medical Informatics, Biometry and Epidemiology, Ludwig-Maximilians-University of Munich, Germany;7. Department of General, Visceral, Transplantation, Vascular and Thoracic Surgery, Klinikum Grosshadern, Ludwig-Maximilians-University of Munich, Germany;1. Hereditary Cancer Program, Catalan Institute of Oncology, IDIBELL, Hospitalet de Llobregat, Spain;2. Unit of Biomarkers and Susceptibility, Catalan Institute of Oncology, IDIBELL and CIBERESP, Hospitalet de Llobregat, Barcelona, Spain;3. Translational Research Laboratory, Catalan Institute of Oncology, IDIBELL, Hospitalet de Llobregat, Spain;4. Department of Clinical Sciences, Faculty of Medicine, University of Barcelona, Hospitalet de Llobregat, Barcelona, Spain;1. Department of Pathology, Western General Hospital, Edinburgh EH4 2XU, UK;2. Department of Histopathology, Algenon-Firth Building, Leeds General Infirmary, Gt George Street, Leeds, UK;3. Research Oncology, Division of Cancer Studies, King’s College London, 3rd Floor, Bermondsey Wing, Guy’s Hospital, Great Maze Pond, London SE1 9RT, UK;4. Van Geest Cancer Centre, School of Science and Technology, Nottingham Trent University, Nottingham NG11 8NS, UK;5. West Midlands Knowledge and Intelligence Team, Public Health England, 1st Floor, 5 St Philip’s Place, Birmingham B3 2PW, UK;6. Nightingale Centre and Genesis Prevention Centre, University Hospital of South Manchester, Southmoor Road, Manchester M23 9LT, UK;7. Cambridge Breast Unit and NIHR Cambridge Biomedical Research Centre, Cambridge University Hospitals NHS Foundation Trust, Box 97, Cambridge Biomedical Campus, Hills Road, Cambridge CB2 0QQ, UK;8. Department of Radiology, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK;9. West of Scotland Breast Screening Service, Stock Exchange Court, 77 Nelson Mandela Place, Glasgow G2 1QT, UK;10. West Midlands Cancer Screening QA Reference Centre, Public Health England, 1st Floor, 5 St Philip’s Place, Birmingham B3 2PW, UK;11. Department of Surgical Oncology, MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA;1. State Key Laboratory of Environmental Aquatic Chemistry, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, P.O. Box 2871, Beijing 100085, PR China;2. College of Fisheries, Huazhong Agricultural University, Wuhan, China |
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| 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 6.4 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. |
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| Keywords: | Gemcitabine hENT1 Pancreatic cancer |
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