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Poster display session

1905 - Strong tumour cytidine deaminase (CDA) staining predicts for improved survival associated with sequential nab-Paclitaxel (nabP) and gemcitabine (GEM) chemotherapy as first line treatment of patients (pts) with metastatic pancreatic adenocarcinoma (mPDAC)

Date

09 Sep 2017

Session

Poster display session

Topics

Cytotoxic Therapy;  Translational Research;  Pancreatic Cancer

Presenters

Philippa Corrie

Citation

Annals of Oncology (2017) 28 (suppl_5): v209-v268. 10.1093/annonc/mdx369

Authors

P. Corrie1, W. Qian1, A. Gopinathan2, M. Williams3, R. Brais1, J.W. Valle4, B. Basu1, S. Falk5, C. Iwuji6, H. Wasan7, D. Palmer8, M. Scott-Brown9, J. Wadsley10, S. Arif11, L. Bax1, P. Bundi1, R. Skells1, A. Neesse12, D. Tuveson13, D. Jodrell1

Author affiliations

  • 1 Addenbrookes Hospital, Cambridge University Hospitals NHS Foundation Trust, CB2 0QQ - Cambridge/GB
  • 2 Cambridge Institute, Cancer Research UK, Cambridge/GB
  • 3 Cambridge Institute, Cancer Research UK, CB2 0RE - Cambridge/GB
  • 4 Medical Oncology, The Christie NHS Foundation Trust, Manchester/GB
  • 5 Oncology, Bristol Haematology and Oncology Centre, BS2 8ED - Bristol/GB
  • 6 Medical Oncology, Leicester Royal Infirmary, LE1 5WW - Leicester/GB
  • 7 Medical Oncology, Hammersmith Hospital, W12 0HS - London/GB
  • 8 Medical Oncology, Clatterbridge Cancer Centre, CH63 4JY - Wirral/GB
  • 9 Medical Oncology, University Hospital Coventry and Warwickshire, CV2 2DX - Coventry/GB
  • 10 Medical Oncology, Weston Park Hospital Cancer Research Centre, S10 2SJ - Sheffield/GB
  • 11 Medical Oncology, Velindre Cancer Centre, CF14 2TL - Cardiff/GB
  • 12 Department Of Gastroenterology, Universitätsmedizin Göttingen - Vorstand, 37075 - Göttingen/DE
  • 13 Cshl Cancer Center, Cold Spring Harbor Laboratory, 11724 - Cold Spring Harbor/US
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Resources

Abstract 1905

Background

NabP+GEM chemotherapy improves survival as treatment for mPDAC, compared with GEM alone. The UK randomised phase 2 SIEGE trial showed that sequential (SEQ) delivery of nabP+GEM (with nabP given 24 hours before GEM) trended towards improved efficacy compared with standard concomitant (CON) delivery. Preclinical models suggest that nabP potentiates GEM activity by either impacting on stroma or reducing CDA levels.

Methods

146 pts were randomised to receive CON or SEQ nabP+GEM. Baseline whole blood (wb) CDA activity was measured using an endpoint read, spectrometric, plate based assay. Baseline tumour IHC assessed stromal content (H&E), CDA (ab137605) and nucleoside transporter protein, hENT1 (Ventana SP120) expression.

Results

6-month (m) progression-free survival (PFS, primary end point) by SEQ and CON arms was 47% and 33%; median PFS was 5.8 and 4.1m (HR 0.68, 95%CI 0.48-0.97); median overall survival (OS) was 10.1 and 7.9m, respectively. Baseline wb CDA activity correlated only with ANC (R2 0.70, p

Conclusions

Whole blood CDA activity was not a useful predictive biomarker, due to the dominant neutrophil effect. Instead, strong tumour CDA expression predicted for pts most likely to have a survival benefit from SEQ therapy and warrants further exploration.

Clinical trial identification

EudraCT Nr: 2013-001868-40 Sponsors Protocol ID: AX-PANC-PI-0101 ISRCTN: ISRCTN71070888

Legal entity responsible for the study

Cambridge University Hospitals NHS Foundation Trust

Funding

Celgene UK

Disclosure

P. Corrie: Funding for the SIEGE clinical trial from Celgene Advisory boards in the last 2 years for BMS, Novartis, MSD, Pierre Fabre, Baxalta. J.W. Valle: Speakers\' Bureau, Travel, acommodations and expenses from Celgene. B. Basu: Research funding and provision of trial drug from Celgene. Travel, accommodation and registration expenses for ASCO and ESMO Congresses from Bayer. Consulting and advisory role with Baxter Healthcare, Astex, Celgene, Nordic. Honararium from BTG Itrnl. H. Wasan: Honoraria, Speakers bureau and research funding from Celgene and Merck KGA. D. Palmer: Honoraria from Celgene, Nucana, BMS, Sirtex, Bayer. J. Wadsley: Honoraria from Celgene for participation in advisory boards, financial support Celgene to attend conferences. D. Jodrell: Receipt of grants/research supports: Support for Educational Symposium (Celgene) Receipt of honoraria or consultation fees: Support for Scientific Meeting attendance (Celgene). All other authors have declared no conflicts of interest.

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