Second-Line Liposomal Irinotecan Plus Fluorouracil/Leucovorin in Metastatic Biliary Tract Cancer

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In an updated analysis of a Korean phase IIb trial (NIFTY) reported in JAMA Oncology, Hyung et al found that the addition of nanoliposomal irinotecan to fluorouracil and leucovorin significantly improved progression-free survival in patients with metastatic biliary tract cancer with disease progression on first-line treatment with gemcitabine/cisplatin.

Study Details

The primary analysis of the trial showed significantly prolonged progression-free survival with the addition of nanoliposomal irinotecan to fluorouracil/leucovorin. The updated analysis included extended follow-up of 1.3 years and performance of masked independent central review by a new team of radiologists. In the multicenter trial, 174 patients (full analysis set) were randomly assigned between September 2018 and December 2021 to receive leucovorin at 400 mg/m2 and fluorouracil at 2,400 mg/m2 via 46-hour infusion every 2 weeks with (n = 88) or without (n = 86) nanoliposomal irinotecan at 70 mg/m2. Treatment continued until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival on masked independent central review.

Key Findings

Median follow-up was 33.2 months (interquartile range = 27.6–35.7 months). Median progression-free survival on masked independent central review was 4.2 months (95% confidence interval [CI] = 2.8–5.3 months) in the nanoliposomal irinotecan group vs 1.7 months (95% CI = 1.4–2.6 months) in the control group (hazard ratio [HR] = 0.61, 95% CI = 0.44–0.86, P = .004). The rate at 6 months was 31.8% (95% CI = 21.7%–41.8%) vs 15.1% (95% CI = 7.5%–22.7%).

On investigator assessment, median progression-free survival was 3.9 months (95% CI = 2.7–5.2 months) in the nanoliposomal irinotecan group vs 1.6 months (95% CI = 1.3–2.2 months in the control group [HR = 0.51, 95% CI = 0.36–0.71, P < .001]). The ratesat 6 months was 30.0% (95% CI = 20.2%–39.8%) vs 11.6% (95% CI = 4.9%–18.4%).

Median overall survival was 8.6 months (95% CI = 5.4–10.5 months) in the nanoliposomal irinotecan group vs 5.3 months (95% CI = 4.7–7.2 months) in the control group (HR = 0.68, 95% CI = 0.48–0.95, P = .02). The rate at 6 months was 60.7% (95% CI = 50.3%–71.2%) vs 44.7% (95% CI = 34.2%–55.3%).

The investigators concluded: “The NIFTY randomized clinical trial demonstrated significant improvement in [progression-free survival] with treatment with [nanoliposomal irinotecan] plus [fluorouracil/leucovorin] compared with [fluorouracil/leucovorin] alone for patients with advanced [biliary tract cancer] after progression to gemcitabine plus cisplatin. The combination of [nanoliposomal irinotecan] plus [fluorouracil/leucovorin] could be considered as a second-line treatment option for patients with previously treated advanced [biliary tract cancer].”

Changhoon Yoo, MD, PhD, of the Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, is the corresponding author of the JAMA Oncology article.

Disclosure: The study was supported by Servier and HK inno.N. For full disclosures of the study authors, visit

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