Fluorouracil and Leucovorin With, Without Nanoliposomal Irinotecan for Cholangiocarcinoma

Results of the NAPOLI-1 trial, which showed the benefits of nanoliposomal irinotecan with fluorouracil and leucovorin for pancreatic ductal adenocarcinoma, inspired researchers to examine the combination in patients with previously treated cholangiocarcinoma in the NALIRICC trial.

Arndt Vogel, MD, PhD, and colleagues compared the triplet combination against fluorouracil with leucovorin alone as a second-line treatment option.

The phase 2 trial enrolled 100 patients between December 2017 and August 2021 with metastatic cholangiocarcinoma who had previously progressed on gemcitabine-based therapy and had an Eastern Cooperative Oncology Group performance status of 0-1.

Each patient was randomly assigned to receive intravenous nanoliposomal irinotecan (70 mg/m²), fluorouracil (2400 mg/m²), and leucovorin (400 mg/m²) every 2 weeks (irinotecan group) or fluorouracil (2400 mg/m²) with leucovorin (400 mg/m²) alone every 2 weeks (control group).

The primary end point was investigator-assessed progression-free survival (PFS). The secondary end points were overall survival (OS), objective response rate (ORR), and quality of life. Safety was assessed in all patients who received at least 1 treatment dose.

A total of 49 patients were enrolled in the irinotecan group, and 51 patients were placed in the control group. The median PFS was 2.6 and 2.3 months in the irinotecan and control groups, respectively. The median OS was 6.9 and 8.2 months, respectively, in the irinotecan and control groups. The ORR was 14% in the irinotecan group and 4% in the control group.

In the irinotecan group, the most common grade 3 or worse adverse events (AEs) were neutropenia (17%), diarrhea (15%), and nausea (8%). In the control group, AEs included cholangitis (8%) and bile duct stenosis (8%).

Serious treatment-related AEs occurred in 33% of patients in the irinotecan group and 2% in the control group. The median duration until deterioration of global health status (defined as the time from randomization to the initial observation of a score decline exceeding 10 points) was 4.0 months (95% CI, 2.2 to not reached) in the irinotecan group and 3.7 months (2.7 to not reached) in the control group.

Adding nanoliposomal irinotecan to fluorouracil plus leucovorin did not improve PFS or OS in patients with cholangiocarcinoma, and the combination had higher toxicity than fluorouracil plus leucovorin alone. Further research is warranted to explore the role of irinotecan-based combinations for the second-line treatment of cholangiocarcinoma.