Steffen Ormanns1, Volker Heinemann2, Mitch Raponi3, Jeff Isaacson3, Rüdiger P Laubender4, Michael Haas5, Stephan Kruger5, Axel Kleespies6, Elaina Mann3, Mike Bartosiewicz3, Thomas Kirchner7, Stefan Boeck8. 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; German Cancer Consortium (DKTK), Heidelberg, Germany; German Cancer Research Center (DKFZ), Heidelberg, Germany. 3. Clovis Oncology Inc., San Francisco, CA, USA. 4. German Cancer Consortium (DKTK), Heidelberg, Germany; German Cancer Research Center (DKFZ), Heidelberg, Germany; Institute of Medical Informatics, Biometry and Epidemiology, Ludwig-Maximilians-University of Munich, Germany. 5. Department of Internal Medicine III and Comprehensive Cancer Center, Klinikum Grosshadern, Ludwig-Maximilians-University of Munich, Germany. 6. Department of General, Visceral, Transplantation, Vascular and Thoracic Surgery, Klinikum Grosshadern, Ludwig-Maximilians-University of Munich, Germany. 7. Department of Pathology, Ludwig-Maximilians-University of Munich, Germany; German Cancer Consortium (DKTK), Heidelberg, Germany; German Cancer Research Center (DKFZ), Heidelberg, Germany. 8. Department of Internal Medicine III and Comprehensive Cancer Center, Klinikum Grosshadern, Ludwig-Maximilians-University of Munich, Germany. Electronic address: stefan.boeck@med.uni-muenchen.de.
Abstract
BACKGROUND: The 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 METHODS: AIO-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. RESULTS:Thirty-nine out of 130 fresh-cut slides were scored as hENT1(high) (30%), whereas 91 samples were classified as hENT1(low) (70%). For the 62 patients randomised to CEG median overall survival was estimated with 6.4 months in the hENT1(low) compared to 6.9 months in the hENT1(high) 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 hENT1(low) compared to 4.4 months in the hENT1(high) subgroup (HR 1.16, 95% CI 0.69-1.96, p=0.57). In 101 patients receivinggemcitabine at any time during study treatment (either within the 1st- or 2nd-line setting) hENT1(low) cases had a median overall survival of 7.5 months and hENT1(high) patients an overall survival of 4.4 months (HR 1.30, 95% CI 0.84-2.03, p=0.24), respectively. CONCLUSION: Within 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.
RCT Entities:
BACKGROUND: The role of humanequilibrative nucleoside transporter 1 (hENT1) as a predictive biomarker for gemcitabine efficacy in advanced pancreatic cancer remains unclear to date. PATIENTS AND METHODS: AIO-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. RESULTS: Thirty-nine out of 130 fresh-cut slides were scored as hENT1(high) (30%), whereas 91 samples were classified as hENT1(low) (70%). For the 62 patients randomised to CEG median overall survival was estimated with 6.4 months in the hENT1(low) compared to 6.9 months in the hENT1(high) 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 hENT1(low) compared to 4.4 months in the hENT1(high) 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) hENT1(low) cases had a median overall survival of 7.5 months and hENT1(high) patients an overall survival of 4.4 months (HR 1.30, 95% CI 0.84-2.03, p=0.24), respectively. CONCLUSION: Within 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.
Authors: A Orlandi; M A Calegari; M Martini; A Cocomazzi; C Bagalà; G Indellicati; V Zurlo; M Basso; A Cassano; L M Larocca; C Barone Journal: Clin Transl Oncol Date: 2016-01-07 Impact factor: 3.405
Authors: Steve E Kalloger; Maziar Riazy; Basile Tessier-Cloutier; Joanna M Karasinska; Dongxia Gao; Renata D Peixoto; Setareh Samimi; Christine Chow; Hui-Li Wong; John R Mackey; Daniel J Renouf; David F Schaeffer Journal: J Pathol Clin Res Date: 2017-07-19
Authors: Victor Hugo Fonseca de Jesus; Marcos Pedro Guedes Camandaroba; Mauro Daniel Spina Donadio; Audrey Cabral; Thiago Pimentel Muniz; Luciana de Moura Leite; Lucas Ferreira Sant'Ana Journal: J Gastrointest Oncol Date: 2018-10