Nanoliposomal Irinotecan With Fluorouracil and Leucovorin Showed Promise for Patients With Advanced Cholangiocarcinoma

According to results from the phase 2 NIFE study, nanoliposomal irinotecan with fluorouracil and leucovorin in the first-line setting demonstrated efficacy and safety among patients with advanced, unresectable cholangiocarcinoma. 

“Although [standard-of-care gemcitabine plus cisplatin] is efficacious, it is not well tolerated by all patients,” stated Thomas J Ettrich, MD, University of Ulm, Germany, and coauthors. “As shown for other solid cancers, nanoliposomal irinotecan added efficacy by an extended plasma half-life, increased intratumoral drug concentration compared with conventional irinotecan, and proved effectiveness in the second-line therapy of advanced [cholangiocarcinoma].” 

This multicenter open-label study enrolled 91 patients with histologically confirmed, locally advanced or metastatic, unresectable cholangiocarcinoma. Patients were randomized on a 1-to-1 basis to receive either 80 mg/m² of nanoliposomal irinotecan with 2400 mg/m² of fluorouracil and 400 mg of leucovorin once every 2 weeks (arm A, n = 49), or standard gemcitabine plus cisplatin once every 3 weeks (arm B, n = 42) until disease progression or unacceptable toxicity. Randomization was stratified by primary site, sex, and WHO performance status. The primary end point was 4-month progression-free survival (PFS) rate. Secondary end points included median PFS, median overall survival (OS), objective response rate (ORR), and safety. 

At a median follow-up of 13.5 months, the 4-month PFS rate was 51% in arm A and 59.5% in arm B. Median PFS was 6.0 months in arm A and 6.9 months in arm B (hazard ratio [HR] 0.85; 95% confidence interval [CI], 0.53 to 1.38; P = .52). Median OS was 15.7 months and 13.6 months, respectively (HR 0.94; 95% CI, 0.58 to 1.50; P = .78). The ORR was 24.5% in arm A and 11.9% in arm B (P = .1780). The safety profile was consistent with prior findings and no unexpected adverse events were reported. In arm A, there were more GI disorders reported including grade 3/4 diarrhea, nausea, and mucositis. In arm B, there were more blood system disorders reported including grade 3/4 neutropenia and anemia.

“NIFE is the first prospective trial demonstrating efficacy of [nanoliposomal irinotecan with fluorouracil and leucovorin] in the first-line therapy setting… and this regimen merits further validation in a larger phase III trial,” concluded Dr Ettrich et al. 

As Journal of Clinical Oncology Associate Editor Eileen O’Reilly, MD, Memorial Sloan Kettering Cancer Center, New York, New York, stated, this study “demonstrates a signal of interest relative to standard of care cisplatin and gemcitabine in a small randomized phase II trial.” 

Source: 

Ettrich TJ, Modest DP, Sinn M, et al. Nanoliposomal irinotecan with fluorouracil and leucovorin or gemcitabine plus cisplatin in advanced cholangiocarcinoma: A phase II study of the AIO hepatobiliary-YMO cancer groups (NIFE-AIO-YMO HEP-0315). J Clin Oncol. Published online: June 6, 2024. doi: 10.1200/JCO.23.01566