Combo Could Be Standard Second-Line Therapy for Advanced Biliary Tract Cancer

Adding liposomal irinotecan (LI) to fluorouracil and leucovorin (FL) significantly improved survival in patients with previously treated, metastatic biliary tract cancer, according to research published in The Lancet Oncology.

In the phase 2b NIFTY trial ( Identifier: NCT03524508), researchers compared second-line LI plus FL with FL alone in patients with metastatic biliary tract cancer that had progressed on gemcitabine plus cisplatin.

There were 174 patients included in the full analysis — 43% with intrahepatic cholangiocarcinoma, 27% with extrahepatic cholangiocarcinoma, and 30% with gallbladder cancer. The patients’ median age was 64 years (range, 37-84 years), and 57% were men. The median duration of first-line treatment with gemcitabine plus cisplatin was 5.1 months.

The patients were randomly assigned to intravenous LI plus FL (88 patients) every 2 weeks or FL alone (86 patients) every 2 weeks. Patients were treated until disease progression or unacceptable toxicity. The median follow-up was 11.8 months.

The median progression-free survival (PFS), by independent review, was significantly longer in the LI-FL arm than in the FL-alone arm — 7.1 months and 1.4 months, respectively (hazard ratio [HR], 0.56; 95% CI, 0.39-0.81; P =.0019). The 6-month PFS rate was 55.7% and 26.2%, respectively.

The median overall survival (OS) was significantly longer in the LI-FL arm than in the FL-alone arm — 8.6 months and 5.5 months, respectively (HR, 0.68; 95% CI, 0.48-0.98; P =.035). The 6-month OS rates were 60.7% and 45.9%, respectively.

The improvements in PFS and OS with LI-FL were clinically meaningful and generally consistent across various subgroups, according to the researchers. In addition, a quality of life analysis showed no significant differences between the treatment arms.

Grade 3-4 adverse events (AEs) occurred more frequently in the LI-FL arm. The most common grade 3-4 AEs were neutropenia (24% in the LI-FL arm and 1% in the FL-alone arm) and fatigue/asthenia (13% and 3%, respectively).

The rate of serious AEs was 42% in the LI-FL arm and 24% in the FL arm. There were no treatment-related deaths in either am.

Taking these results together, the researchers concluded that LI plus FL “could be considered a standard-of-care second-line therapy for advanced biliary tract cancer.”

Disclosures: This research was supported by Servier and HK inno.N. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Yoo C, Kim KP, Jeong JH, et al. Liposomal irinotecan plus fluorouracil and leucovorin versus fluorouracil and leucovorin for metastatic biliary tract cancer after progression on gemcitabine plus cisplatin (NIFTY): A multicentre, open-label, randomised, phase 2b study. Lancet Oncol. Published online October 14, 2021. doi:10.1016/S1470-2045(21)00486-1