In a French phase II trial (PANOPTIMOX-PRODIGE) reported in the Journal of Clinical Oncology, Dahan et al found that 4 months of FOLFIRINOX (fluorouracil, leucovorin, irinotecan, oxaliplatin) followed by leucovorin/fluorouracil maintenance was associated with favorable outcomes vs 6 months of FOLFIRINOX alone or sequential FOLFIRI.3 (fluorouracil, leucovorin, irinotecan) and gemcitabine in the first-line treatment of metastatic pancreatic cancer.
Study Details
In the open-label, multicenter trial, 273 patients were randomly assigned 1:1:1 between January 2015 and November 2016 to receive:
- Six months of FOLFIRINOX (maximum of 12 14-day cycles; n = 91)
- Four months of FOLFIRINOX followed by leucovorin/fluorouracil maintenance every 14 days until disease progression in patients with controlled disease after eight cycles (n = 92)
- Sequential treatment with FOLFIRI.3 every 14 days for 2 months (4 cycles) followed by two cycles of gemcitabine once a week for 3 of every 4 weeks (n = 90)
The primary endpoint was progression-free survival at 6 months. No statistical comparisons were performed.
Key Findings
A total of 52 patients in the FOLFIRINOX plus maintenance group received leucovorin/fluorouracil maintenance.
Progression-free survival at 6 months was 47.1% in the FOLFIRINOX group, 42.9% in the FOLFIRINOX plus maintenance group, and 34.1% in the sequential FOLFIRI.3/gemcitabine group.
Median overall survival was 10.1 months in the FOLFIRINOX group, 11.2 months in the maintenance group, and 7.3 months in the sequential group. Median survival without deterioration in quality-of-life scores on the EORTC Quality of Life Questionnaire C30 was 7.2 months in the FOLFIRINOX group, 11.4 months in the maintenance group, and 7.5 months in the sequential group.
Hematologic and nonhematologic toxicities were similar in the three groups, except for neurotoxicity. The median dose intensity of oxaliplatin was 83% in the FOLFIRINOX group and 92% in the maintenance group. Grade 3 or 4 neurotoxicity occurred in 10.2% of patients in the FOLFIRINOX group vs 19.8% in the maintenance group.
The investigators concluded, “Maintenance with leucovorin plus fluorouracil appears to be feasible and effective in patients with metastatic pancreatic cancer controlled after 4 months of induction chemotherapy with FOLFIRINOX. Severe neurotoxicity was higher in the maintenance therapy arm, probably because of the higher cumulative dose of oxaliplatin.”
Laetitia Dahan, MD, PhD, of the Department of Digestive Oncology, La Timone, Aix Marseille Université, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by the Fédération Française de Cancérologie Digestive (FFCD). For full disclosures of the study authors, visit ascopubs.org.
