2018 ASCO: Adjuvant mFOLFIRINOX vs Gemcitabine in Resected Pancreatic Cancer
In a randomized phase III trial, patients with surgically removed pancreatic cancer who received mFOLFIRINOX (a modified regimen containing oxaliplatin, leucovorin, irinotecan, and fluorouracil) lived a median of 20 months longer and were cancer-free 9 months longer than those who received the current standard of care, gemcitabine. The study was featured in a press briefing today and presented by Conroy et al at the 2018 ASCO Annual Meeting (Abstract LBA4001).
“For the first time, our trial shows a large benefit from adjuvant FOLFIRINOX chemotherapy over standard chemotherapy with gemcitabine, showing we can help patients with pancreatic cancer live much longer,” said lead study author Thierry Conroy, MD, a medical oncologist and Director of the Institut de Cancerologie de Lorraine in Nancy, one of the UNICANCER Comprehensive Cancer Centers in France. “In addition, we were encouraged to see that the results were better than expected when we planned this trial.”
After pancreatic cancer surgery, adjuvant chemotherapy with gemcitabine can substantially prolong survival compared to surgery alone, as well as increase the number of patients who will probably not relapse from pancreatic cancer (at 5 years, about 21% with gemcitabine vs 10% with surgery alone). Gemcitabine has been the standard adjuvant therapy for the past 10 years.
About the Study
The PRODIGE 24/CCTG PA.6 trial enrolled patients with nonmetastatic pancreatic ductal adenocarcinoma who had surgery that removed all or nearly all of the tumor (meaning no cancer cells visible to the surgeon after surgery, but microscopic tumoral cells may have remained).
At 3 to 12 weeks after surgery, 493 patients were randomly assigned in France and Canada to receive either gemcitabine or mFOLFIRINOX for 6 months. A regimen very similar to mFOLFIRINOX is already used as an initial treatment for metastatic pancreatic cancer, and this study shows FOLFIRINOX can also benefit patients with earlier-stage disease.
Key Findings
At a median follow-up of 33.6 months, the median disease-free survival was much longer in the mFOLFIRINOX group than in the gemcitabine group (21.6 vs 12.8 months), as was the median overall survival (54.4 vs 35.0 months). The benefit of the mFOLFIRINOX was observed in all patient subgroups. mFOLFIRINOX also markedly extended the time until metastases appeared (median = 30.4 months vs 17.0 months with gemcitabine).
Overall, more patients experienced severe side effects (mainly hematologic) in the mFOLFIRINOX group than in the gemcitabine group (76% vs 53%), but the side effects were manageable, according to the authors. One treatment-related death occurred in the gemcitabine group, and none occurred in the mFOLFIRINOX group.
The types of side effects also differed between the two groups. The most common side effects of gemcitabine were headache, fever, flu-like symptoms, swelling, and leukopenia. Patients who received mFOLFIRINOX had more diarrhea, nausea, vomiting, and fatigue. There was no difference in the risk of febrile neutropenia between the two groups.
A past history of ischemic heart disease represents a risk with either regimen, but particularly mFOLFIRINOX. Patients should be assessed for underlying heart disease before starting this adjuvant treatment, a precaution that is routine for many people with cancer receiving surgery and chemotherapy.
Next Steps
The next step will be to explore the timing of chemotherapy. Patients may benefit from neoadjuvant chemotherapy to destroy undetectable micrometastases and increase the chance that the tumor can be completely removed through surgery. Dr. Conroy noted that mFOLFIRINOX appears to be a good candidate for neoadjuvant chemotherapy. Another option is to give perioperative chemotherapy. Ongoing clinical trials are already testing both of these approaches.
This study, sponsored by UNICANCER, Paris, received funding from the Institut National du Cancer in France, French National League Against Cancer, Canadian Cancer Society, and “7 Days in May,” a charity cycling event in Canada.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
