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  • Oncological Management of Pancreatic

    Cancer

    Pancreatic Cancer UK National Study Day

    Yuk Ting Ma Senior Clinical Lecturer & Honorary Consultant in

    Hepatobiliary Oncology

  • Outline of talk

    • Current treatment

    • Adjuvant

    • Locally advanced

    • Metastatic disease

    • Developing areas of work

    • Neoadjuvant chemotherapy

    • Personalised medicine

    • Immunotherapy

  • Early Locally advanced Metastatic

    15% 50%35%

    Staging

  • ADJUVANT CHEMOTHERAPY

  • Rationale for adjuvant therapy

    • 80% will relapse within 1-2 years of surgery

    • Disease progression occurs at both local and distant sites

  • ESPAC1 ESPAC3

    Chemo No Chemo HR P value

    Median survival 20.1 mths 15.5 mths 0.71

    (0.55-0.92)

    P=0.09

    5 year survival 21% 8%

    5FU Gem HR P value

    Median survival 23 mths 23.6 mths 0.94

    (0.81-1.08)

    P=0.39

    5 year survival 21% 8%

    N Engl J Med 2004;350(12):1200-10. JAMA 2010;304(10):1073-81.

  • Toxicity

    JAMA 2010;304(10):1073-81.

  • ESPAC4 Gem Cap Gem HR P value

    Median survival 28 mths 25.5 mths 0.82

    (0.68-0.98)

    P=0.032

    5 year survival 28.8% 16.3%

    Lancet 2017;389:1011-1024.

  • Optimal duration and timing of adjuvant chemo

    J Clin Oncol 2014;32:504-512

    • Overall survival favours those who

    complete all six cycles of treatment

    (HR 0.52; 95% CI (0.44-0.60);

    p

  • Beyond 12 weeks?

    Ann Surg Oncol 2017; 24:2770-2776

  • NICE guidance

  • Adjuvant FOLFIRINOX FOLFIRINOX Gem HR P value

    Median survival 54.4 mths 35 mths 0.64

    (0.48-0.86)

    P

  • METASTATIC PANCREATIC CANCER

  • J Clin Oncol 1997;15(6):2403-13

    Gemcitabine Gem 5FU P value

    Clinical benefit response 23.8% 4.8% P=0.0022

    Median survival 5.65 mths 4.41 mths P=0.025

    12 month survival 18% 2%

  • N Engl J Med 2011;364(19):1817-25

    FOLFIRINOX FOLFIRINOX Gem HR P value

    Median survival 11.1 mths 6.8 mths 0.57

    (0.45-0.73)

    P

  • N Engl J Med 2011;364(19):1817-25

  • Toxicity G3/4

    N Engl J Med 2011;364(19):1817-25

  • N Engl J Med 2013; 369(18):1691-703

    Gemcitabine/Abraxane

    Gem/Abraxane Gem HR P value

    Median

    survival

    8.5 mths 6.7 mths 0.72

    (0.62-0.83)

    P

  • N Engl J Med 2013; 369(18):1691-703

  • N Engl J Med 2013; 369(18):1691-703

  • NICE guidance

  • LOCALLY ADVANCED DISEASE

  • Chemotherapy

    • Response rates combination chemo higher than gemcitabine

    alone

    • FOLFIRINOX

    • Gemcitabine combination

    • Gemcitabine

  • LAP07 Chemo only Chemo + ChemoRT HR P value Median survival 16.5 mths 15.2 mths 1.03

    (0.79-1.34)

    P=0.83

    JAMA 2016;315:1844-1853

  • Which radiosensitiser?....SCALOP

    Lancet Oncol 2013;14:317-326

  • NICE guidance

  • DEVELOPING AREAS OF WORK

  • Downstaging chemotherapy

    Early Locally advanced Metastatic

    Downstaging

    chemotherapy

  • • Conversion from unresectable or borderline resectable

    state to resectable disease

    • Increase rate of R0 resections

    Downstaging chemotherapy

  • • Not a new approach!

    Downstaging chemotherapy

  • • All retrospective and prospective studies of neoadjuvant therapy

    in patients with pancreatic or periampullary cancers (1980-2009)

    • 111 studies (4,394 patients)

    Systematic review

    PLoS Med 2010; 7(4): e1000267

  • • All retrospective and prospective studies of neoadjuvant therapy

    in patients with pancreatic or periampullary cancers (1980-2009)

    • 111 studies (4,394 patients)

    • Patients who become resectable after neoadjuvant therapy

    have comparable survival to those who were initially

    resectable

    Systematic review

    PLoS Med 2010; 7(4): e1000267

  • • Improved imaging – high resolution CT/MRI

    • Improved surgery – vascular resection

    • Improved chemotherapy

    Downstaging chemo – a renaissance

  • Personalised medicine

    http://www.google.co.uk/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=&url=http://www.precisionpanc.org/&psig=AOvVaw0HhkdlpNfxQtKGgRlgGy7c&ust=1539341331229447 http://www.google.co.uk/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=&url=http://www.precisionpanc.org/&psig=AOvVaw0HhkdlpNfxQtKGgRlgGy7c&ust=1539341331229447

  • PRECISION PANC

  • Immunotherapy…is there a role?

    Trends in Cancer 2018;4:418-428

  • Summary

    • Current standard of care treatment informed by evidence base

    and endorsed by NICE guidelines.

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