A clinical trial has shown that 29% of pancreatic cancer patients given a combination of two chemotherapy drugs lived for at least five years, compared with 16% who received only the one drug.
The latest Cancer Research UK figures show that around 9,400 people are diagnosed with pancreatic cancer each year in the UK and around 8,800 people die from the disease each year.
The trial involved 732 patients in hospitals across the UK, Germany, Sweden and France who had undergone surgery to remove their tumour. Around half of patients on the trial received one chemotherapy drug, gemcitabine, and the other half received a combination of chemotherapy drugs, gemcitabine and capecitabine.
At this time the standard treatment for patients who have undergone surgery is for them to be administered gemcitabine alone.
According to the study 29% of the patients given a combination of the two chemotherapy drugs lived for at least five years compared with only 16% of patients given gemcitabine alone.
The study states that this new combination of drugs approach should be the new standard of care for pancreatic cancer patients who have had surgery to remove their tumour.
This trial was originally set up in 2008 to address the poor pancreatic cancer survival rates.
The results, which were first presented at the American Society of Clinical Oncology (ASCO) in June 2016 but have now been peer-reviewed, show that this treatment plan is predicted to double the number of patients who survive their disease for at least five years.
Trial lead, Professor John Neoptolemos at the University of Liverpool’s Institute of Translational Medicine, and director of the Liverpool Clinical and Cancer Research UK Trials Unit, said: “This is one of the biggest ever breakthroughs prolonging survival for pancreatic cancer patients. When this combination becomes the new standard of care around the world, it will give many patients living with the disease valuable months and even years.”
Professor Peter Johnson, Cancer Research UK’s chief clinician, said: “Pancreatic cancer is a notoriously difficult disease to treat. Nearly 10,000 patients are diagnosed each year in the UK so we urgently need new ways to treat and manage the disease. Research that tells us more about how the disease grows and spreads – and trials like this one – will be key to improve survival for patients living with the disease.”
Summary
Background: The ESPAC-3 trial showed that adjuvant gemcitabine is the standard of care based on similar survival to and less toxicity than adjuvant 5-fluorouracil/folinic acid in patients with resected pancreatic cancer. Other clinical trials have shown better survival and tumour response with gemcitabine and capecitabine than with gemcitabine alone in advanced or metastatic pancreatic cancer. We aimed to determine the efficacy and safety of gemcitabine and capecitabine compared with gemcitabine monotherapy for resected pancreatic cancer.
Methods: We did a phase 3, two-group, open-label, multicentre, randomised clinical trial at 92 hospitals in England, Scotland, Wales, Germany, France, and Sweden. Eligible patients were aged 18 years or older and had undergone complete macroscopic resection for ductal adenocarcinoma of the pancreas (R0 or R1 resection). We randomly assigned patients (1:1) within 12 weeks of surgery to receive six cycles of either 1000 mg/m2 gemcitabine alone administered once a week for three of every 4 weeks (one cycle) or with 1660 mg/m2 oral capecitabine administered for 21 days followed by 7 days' rest (one cycle). Randomisation was based on a minimisation routine, and country was used as a stratification factor. The primary endpoint was overall survival, measured as the time from randomisation until death from any cause, and assessed in the intention-to-treat population. Toxicity was analysed in all patients who received trial treatment. This trial was registered with the EudraCT, number 2007-004299-38, and ISRCTN, number ISRCTN96397434.
Findings: Of 732 patients enrolled, 730 were included in the final analysis. Of these, 366 were randomly assigned to receive gemcitabine and 364 to gemcitabine plus capecitabine. The Independent Data and Safety Monitoring Committee requested reporting of the results after there were 458 (95%) of a target of 480 deaths. The median overall survival for patients in the gemcitabine plus capecitabine group was 28·0 months (95% CI 23·5–31·5) compared with 25·5 months (22·7–27·9) in the gemcitabine group (hazard ratio 0·82 [95% CI 0·68–0·98], p=0·032). 608 grade 3–4 adverse events were reported by 226 of 359 patients in the gemcitabine plus capecitabine group compared with 481 grade 3–4 adverse events in 196 of 366 patients in the gemcitabine group.
Interpretation: The adjuvant combination of gemcitabine and capecitabine should be the new standard of care following resection for pancreatic ductal adenocarcinoma.
Authors
John P Neoptolemos, Daniel H Palmer, Paula Ghaneh, Eftychia E Psarelli, Juan W Valle,
Christopher M Halloran, Olusola Faluyi, Derek A O'Reilly, David Cunningham, Jonathan Wadsley, Suzanne Darby, Tim Meyer, Roopinder Gillmore, Alan Anthoney, Per Lind, Bengt Glimelius, Stephen Falk, Jakob R Izbicki, Gary William Middleton, Sebastian Cummins, Paul J Ross, Harpreet Wasan, Alec McDonald, Tom Crosby, Yuk Ting Ma, Kinnari Patel, David Sherriff, Rubin Soomal, David Borg, Sharmila Sothi, Pascal Hammel, Thilo Hackert, Richard Jackson, Markus W Büchler
[link url="https://news.liverpool.ac.uk/2017/01/25/new-approach-improves-five-year-survival-for-pancreatic-cancer-patients/"]University of Liverpool material[/link]
[link url="http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(16)32409-6/fulltext"]The Lancet article summary[/link]