Nanoliposomal irinotecan combined with fluorouracil and folinic acid (leucovorin) extends survival in patients with metastatic pancreatic ductal adenocarcinoma who had previously been treated with gemcitabine-based therapy compared with nanoliposomal irinotecan alone, a global, randomized, phase 3, open-label trial has found.1
The research was based on a phase 2 trial that found that nanoliposomal irinotecan showed activity in patients with metastatic pancreatic ductal adenocarcinoma who had been treated with gemcitabine-based therapies.2
The phase 3 trial enrolled 417 patients at 76 centers in 14 countries between January 2012, and September 2013. The patients were randomly assigned to one of 3 arms and received either nanoliposomal irinotecan with fluorouracil and folinic acid, nanoliposomal irinotecan only, or fluorouracil and leucovorin only.
The primary endpoint of the study was overall survival. Secondary endpoints included progression-free survival, time to treatment failure, the proportion of patients achieving an objective response, and clinical benefit response. Median overall survival in the group that received nanoliposomal irinotecan combined with fluorouracil and folinic acid was more than 1 month longer than those receiving nanoliposomal irinotecan only, and it was nearly 2 months longer than those receiving fluorouracil and folinic acid only.
“Nab-paclitaxel plus gemcitabine, the current standard frontline therapy, could achieve 5.5 months of median progression-free survival, 8.5 months of overall survival, and a 35% 12-month survival rate in chemo-naive metastatic pancreatic cancer patients,” Li-Tzong Chen, MD, the director of the National Institute of Cancer Research at the National Health Research Institutes in Taiwan, told Cancer Therapy Advisor.
Dr. Chen explained that this regimen is the first approved second-line therapy for patients with metastatic pancreatic cancer previously treated with gemcitabine-based therapy. The therapy has a 16% response rate, 3.1 months of progression-free survival, and 6.1 months of overall survival.
“Because nab-paclitaxel plus gemcitabine is the current standard of care in chemotherapy-naive metastatic pancreatic cancer patients, nanoliposomal irinotecan plus fluorouracil and folinic acid will definitely be a better second-line choice than the oxaliplatin-containing regimens, because nanoliposomal irinotecan has no overlapping sensory neuropathy adverse events,” said Dr Chen. Neurotoxicity is the most frequent dose-limiting side effect of oxaliplatin.3
The most common grade 3 and 4 adverse events in patients who received nanoliposomal irinotecan plus fluorouracil and folinic acid were neutropenia (27%), diarrhea (13%), vomiting (11%), and nausea (8%). Among patients who received nanoliposomal irinotecan alone, the most common grade 3 and 4 adverse events were diarrhea (21%), decreased appetite (19%), neutropenia (15%), and vomiting (14%).
“The introduction of such a tolerable, effective, and non–cross-resistant combination regimen will definitively improve the clinical outcomes of patients with metastatic pancreatic cancer,” Dr Chen concluded.
A randomized, phase 2 trial comparing nanoliposomal irinotecan plus fluorouracil/leucovorin-based regimens with nab-paclitaxel plus gemcitabine as a frontline therapy for patients with metastatic pancreatic cancer is ongoing.
- Wang-Gillam A, Li CP, Bodoky G, et al. Nanoliposomal irinotecan with fluorouracil and folinic acid in metastatic pancreatic cancer after previous gemcitabine-based therapy (NAPOLI-1): a global, randomised, open-label, phase 3 trial [published online ahead of print November 29, 2015]. The Lancet. doi: 10.1016/S0140-6736(15)00986-1.
- Ko AH, Tempero MA, Shan YS, et al. A multinational phase 2 study of nanoliposomal irinotecan sucrosofate (PEP02, na1-IRI) for patients with gemcitabine-refractory metastatic pancreatic cancer. Br J Cancer. 2013;109(4):920-925.
- Saif MW, Reardon J. Management of oxaliplatin-induced peripheral neuropathy. Ther Clin Risk Manag. 2015;1(4): 249-258.