Thierry Conroy, MD
In results of the PRODIGE 24/CCTG PA.6 trial presented at the 2018 ASCO Annual Meeting and again at the World Congress on Gastrointestinal Cancers, a modified FOLFIRINOX (mFOLFIRINOX) regimen was superior to the standard of care, gemcitabine, as postoperative therapy in patients with resected pancreatic cancer.
In 493 patients with nonmetastatic pancreatic ductal adenocarcinoma, a median overall survival (OS) of 54.4 months was found with mFOLFIRINOX, compared with 35.0 months with gemcitabine. With an OS over 20 months longer than the standard of care, this treatment regimen also reduced the risk of death by 36%.
Compared with gemcitabine, the mFOLFIRINOX regimen was more toxic than the standard of care, but the toxicities found were more manageable. However, according to lead author Thierry Conroy, MD, who presented the data at both meetings, this regimen clearly improves survival in patients with resected pancreatic cancer and should be considered the new standard of care.
In an interview with OncLive
, Conroy, a medical oncologist and director of the Institut de Cancerologie de Lorraine in Nancy, France, discussed this trial in further detail and shared his insight on future research with this treatment regimen.
OncLive: Can you share some background on the rationale for this study?
: This study is a multicenter trial of adjuvant chemotherapy. As you know, gemcitabine has been the standard of care since ASCO 2008 when fluorouracil (5-FU) plus folinic acid had the same survival results and this improved survival after surgery alone and adjuvant treatment used for 6 months. In France, we developed the FOLFIRINOX regimen, which is oxaliplatin, leucovorin, irinotecan, and 5-FU in a continuous infusion, which was demonstrated as superior to gemcitabine in metastatic disease and published in the New England Journal of Medicine
in 2010. However, FOLFIRINOX may be a bit toxic for adjuvant use, so we suppress from the regimen the bolus 5-FU and only use continuous infusion of 5-FU with the other drugs. In this study, we've compared the modified FOLFIRINOX (mFOLFIRINOX), which has the same efficacy in metastatic disease, to the standard of care, gemcitabine, 3-12 weeks after surgery. Both regimens were given to the patients for 6 months.
What were the results?
We included 493 patients within 77 centers in Canada and France, because it's a joint protocol between 3 groups which are part of PRODIGE in France and the CTCG in Canada. We included patients with ductal pancreatic adenocarcinoma with any kind of complete resection of 0 or 1. We had a median follow-up of 43.6 months, which is relatively short. This is due to the fact that independent data monitoring committee decided in February that we should present and publish this trial as soon as possible for ethical reasons.
The results show first that mFOLFIRINOX is a safe regimen, but it's more toxic than gemcitabine. FOLFIRINOX gives significantly more diarrhea, mucositis, and hand-foot syndrome. It also gives 11% grade 3 fatigue. Gemcitabine gives, most significantly, more thrombocytopenia, more headache, more flu-like symptoms, and an increase in transaminase. There was no difference in febrile neutropenia between both groups, however, regrettably, we had 1 toxic death in the gemcitabine arm. There were no deaths in the mFOLFIRINOX group.
The main objective of the trial was disease-free survival (DFS). There is a very important increase in DFS in favor of patients treated with mFOLFIRINOX. It almost doubled the 3-year DFS, so these are very important results for the patients. We also had a clear reduction in the metastases rate – more than 40% – and a survival benefit, with a median survival of more than 54 months in the mFOLFIRINOX group as compared to 35 months in the gemcitabine group. This is highly significant at 3 years. Looking only at death from cancer, there's a 15% increase in survival at 3 years in the group treated with mFOLFIRINOX.