Comparison of Liposomal Irinotecan (nal-IRI) plus 5-Fluorouracil/Leucovorin (5-FU/LV) versus Gemcitabine/Cisplatin as First-Line Therapy in Patients with Advanced Biliary Tract Cancer: The NIFE Trial

Clinical outcomes in advanced biliary tract cancer (BTC) are modest with the current standard of care gemcitabine/cisplatin. The NIFE study examined nanoliposomal-irinotecan (nal-IRI)/5-fluorouracil (5-FU)/leucovorin (LV) as an alternative first-line treatment option in advanced BTC.

NIFE was a prospective, randomized, 2-sided, phase 2 study in which 93 patients with advanced BTC in 21 centers in Germany were randomized (1:1) to receive either nal-IRI/5-FU/LV (arm A) or gemcitabine/cisplatin (arm B), with a stratification for tumor site (intrahepatic vs extrahepatic), gender, and Eastern Cooperative Oncology Group performance status (0 vs 1). Arm A was planned as a Simon’s optimal 2-stage design and arm B served as an internal control for selection bias. The primary end point was defined as the 4-month progression-free survival (PFS) rate ≥50% in the intent-to-treat (ITT) population.

The NIFE trial met its primary end point with a PFS rate of 51% at 4 months in the ITT population (arm A). Median PFS in arm A was 5.98 months (95% confidence interval [CI], 2.37-9.59) and 6.87 months (95% CI, 2.46-7.82) in arm B. Provisional median overall survival (OS) was 15.9 months (95% CI, 10.58-21.85) in arm A and 13.63 months (95% CI, 6.51-17.68) in arm B with ongoing follow-up at data closure.

Median PFS in intrahepatic cholangiocarcinoma (CCA) versus extrahepatic CCA was 3.45 months (95% CI, 2.10-6.05) versus 9.59 months (95% CI, 1.94-15.67) in arm A, and 7.72 months (95% CI, 6.05-9.46) versus 1.76 months (95% CI, 0.16-6.87) in arm B. Corresponding median OS was 14.19 months for intrahepatic CCA and 18.23 months for extrahepatic CCA in arm A; and 16.36 months for intrahepatic CCA and 6.34 months for extrahepatic CCA in arm B.

The investigators concluded that nal-IRI/5-FU/LV showed efficacy as first-line treatment of advanced BTC with no new safety findings. Extrahepatic CCA and intrahepatic CCA responded differently to drug interventions, with a clear benefit for nal-IRI/5-FU/LV in extrahepatic CCA.

Source

Perkhofer L, Striefler JK, Sinn M, et al. Nal-IRI with 5-fluorouracil (5-FU) and leucovorin or gemcitabine plus cisplatin in advanced biliary tract cancer: final results of the NIFE-trial (AIO-YMO HEP-0315), a randomized phase II study of the AIO biliary tract cancer group. Ann Oncol. 2021;32(suppl_5):S1283-S1346.