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. 2024 Sep 10;42(26):3094-3104. doi: 10.1200/JCO.23.01566. Epub 2024 Jun 6.

Abstract

Purpose: First-line therapy options in advanced cholangiocarcinoma (CCA) are based on the ABC-02 trial regimen (gemcitabine/cisplatin [G/C]). The NIFE trial examined nanoliposomal irinotecan/fluorouracil/leucovorin (nal-IRI/FU/LV) as alternative first-line therapy in advanced CCA.

Methods: NIFE is a prospective, open-label, randomized, multicenter phase II study that aimed at detecting efficacy comparable with the standard treatment. Patients with advanced CCA were randomly assigned (1:1) to receive nal-IRI/FU/LV (arm A) or G/C (arm B). Stratification parameters were intrahepatic versus extrahepatic CCA, sex, and Eastern Cooperative Oncology Group (ECOG; 0/1). Arm A was designed as a Simon's optimal two-stage design and arm B served as a randomized control group. The primary goal was to exclude an inferior progression-free survival (PFS) at 4 months of only 40%, while assuming a rate of 60% on G/C population.

Results: Between 2018 and 2020, overall 91 patients were randomly assigned to receive nal-IRI/FU/LV (n = 49) or G/C (n = 42). The NIFE trial formally met its primary end point with a 4-month PFS rate of 51% in patients receiving nal-IRI/FU/LV. The median PFS was 6 months (2.4-9.6) in arm A and 6.9 months (2.5-7.9) in arm B. Median overall survival (OS) was 15.9 months (10.6-20.3) in arm A and 13.6 months (6.5-17.7) in arm B. The exploratory comparison of study arms suggested a numerical but statistically not significant advantage for nal-IRI/FU/LV (hazard ratio for PFS, 0.85 [95% CI, 0.53 to 1.38] and for OS, 0.94 [95% CI, 0.58 to 1.50]). Analysis for stratification parameters revealed no differences for sex and ECOG, but for tumor localization. The objective response rate was 24.5% with nal-IRI/FU/LV and 11.9% with G/C. No unexpected toxicities occurred. AEs related to nal-IRI/FU/LV were mainly GI and to G/C hematologic.

Conclusion: Treatment of advanced CCA with nal-IRI/FU/LV demonstrated efficacy in first-line therapy without new safety findings and merits further validation.

Trial registration: ClinicalTrials.gov NCT03044587.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols* / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • Bile Duct Neoplasms* / drug therapy
  • Bile Duct Neoplasms* / pathology
  • Cholangiocarcinoma* / drug therapy
  • Cholangiocarcinoma* / pathology
  • Cisplatin* / administration & dosage
  • Cisplatin* / adverse effects
  • Deoxycytidine* / administration & dosage
  • Deoxycytidine* / adverse effects
  • Deoxycytidine* / analogs & derivatives
  • Female
  • Fluorouracil* / administration & dosage
  • Gemcitabine*
  • Humans
  • Irinotecan* / administration & dosage
  • Irinotecan* / adverse effects
  • Leucovorin* / administration & dosage
  • Leucovorin* / adverse effects
  • Liposomes*
  • Male
  • Middle Aged
  • Progression-Free Survival
  • Prospective Studies

Substances

  • Gemcitabine
  • Leucovorin
  • Fluorouracil
  • Irinotecan
  • Deoxycytidine
  • Cisplatin
  • Liposomes

Associated data

  • ClinicalTrials.gov/NCT03044587