Oncological Management of Pancreatic
Cancer
Pancreatic Cancer UK National Study Day
Yuk Ting MaSenior 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.
ESPAC4Gem 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<0.01)
• No difference in survival if chemo
delayed up to 12 weeks
(HR 0.99; 95% CI (0.95-1.02))
Beyond 12 weeks?
Ann Surg Oncol 2017; 24:2770-2776
NICE guidance
Adjuvant FOLFIRINOXFOLFIRINOX Gem HR P value
Median survival 54.4 mths 35 mths 0.64
(0.48-0.86)
P<0.003
3 year OS 63.4% 48.6%
Conroy T, ASCO 2018
METASTATIC PANCREATIC CANCER
J Clin Oncol 1997;15(6):2403-13
GemcitabineGem 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
FOLFIRINOXFOLFIRINOX Gem HR P value
Median survival 11.1 mths 6.8 mths 0.57
(0.45-0.73)
P<0.001
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<0.001
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
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.
