Controlled phase III trial of adjuvant combination chemotherapy of gemcitabine and capecitabine, versus monotherapy gemcitabine in patients with resected pancreatic ductal adenocarcinoma

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Published: 3 Jun 2016
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Prof John P. Neoptolemos - University of Liverpool, Liverpool, UK

Prof Neoptolemos presents at ASCO 2016, a European phase III trial, one of the largest ever conducted in pancreatic cancer, which showed that adding the oral drug capecitabine chemotherapy to gemcitabine prolongs survival without increased toxicity.

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ASCO 2016

Controlled phase III trial of adjuvant combination chemotherapy of gemcitabine and capecitabine, versus monotherapy gemcitabine in patients with resected pancreatic ductal adenocarcinoma

Prof John P. Neoptolemos - University of Liverpool, Liverpool, UK


Thank you very much for the introduction. Ladies and gentlemen of the press, good afternoon. It’s a great pleasure to present these results on behalf of the European Study Group for Pancreas Cancer, this is our fourth major trial.

What about pancreas cancer? Well more patients are now dying from pancreas cancer than breast cancer in the United States. Globally there are 338,000 new cases, almost a similar number of deaths. Some progress is being made and we’re beginning to see some clear water now between the number of new cases being diagnosed and the actually number of deaths. So in the United States of America 53,000 new cases in 2016 from ASCO’s own data, and nearly 42,000 deaths. Breast cancer deaths now amount to just under 41,000 so this has moved up to be a really lethal cancer in the scheme of things. These are data from Cancer Research UK in the United Kingdom and you can see that even the one year survival rate has doubled in the last thirty years, principally in the last few years from the greater use of chemotherapy. These data include those 40% of patients who don’t receive any treatment at all because they present either too advanced or with too much of a poor performance status.

The ESPAC-1 trial showed that if you just did surgery and nothing else, did not give chemotherapy or gave chemoradiotherapy, your chances of living of five years were 10% or less. ESPAC-1 established that giving 5-fluorouracil that this jumped up to about 16% and this was confirmed in ESPAC-3 in using gemcitabine with gemcitabine having the lower toxicity of the two. So this was our first step change that took place in the treatment of resected pancreatic cancer.

ESPAC-4 put forward the proposal that combining an oral fluoropyrimidine, in other words 5-FU is given intravenously, capecitabine can be taken orally, that if we can combine the two we might get better results. We calculated that to do this we would need 722 patients. These were randomised at the Liverpool Cancer Trials Unit as a fairly simple trial design. Chemotherapy was given for six months in both arms with three months follow-up rate. We opened 92 sites over six countries and we recruited ahead of target. As it turned out, we were asked to declare the results of ESPAC-4 before we reached the target number of deaths.

Looking at the results, first in terms of complications, there were no complications, meaning serious adverse events between the single arm or the combined arm group of patients. In terms of treatment related, in other words chemotherapy related, events again globally there was no difference between the two arms. This is important given the fact that one arm is combination chemotherapy.

The second part of the result shows that the five year survival rate increased from 16% with gemcitabine to 29% with surgery plus capecitabine. This result is statistically significant.

In conclusion, adjuvant gemcitabine with capecitabine is the second step change that we can now observe for resected pancreas cancer. So if I take you back to ESPAC-1 – surgery with no chemotherapy or radiation therapy, this is with chemotherapy using a single agent and now we have a double agent and you can see the improvement has taken place. The toxicity was acceptable and manageable. The five year survival rate is now 29% and this is now the standard of care for resected pancreatic cancer. Thank you.