Based on the results of the multicenter phase II NIFE-AIO-YMO HEP-0315 trial, which were reported in the Journal of Clinical Oncology by Ettrich et al, first-line palliative treatment with nanoliposomal irinotecan plus fluorouracil and leucovorin appears to be safe and active in patients with advanced cholangiocarcinoma.

“First-line therapy options are based on the ABC-02 trial regimen of gemcitabine plus cisplatin,” the investigators commented. “This trial examined nanoliposomal irinotecan plus fluorouracil and leucovorin as an alternative.”

Study Details

Between 2018 and 2020, patients with nonresectable locally advanced or metastatic cholangiocarcinoma from 21 German centers were randomly assigned 1:1 to receive nanoliposomal irinotecan plus fluorouracil and leucovorin (n = 49) or standard chemotherapy with gemcitabine plus cisplatin (n = 42). Stratification factors included primary disease location (intrahepatic vs extrahepatic), sex, and Eastern Cooperative Oncology Group (ECOG) performance status score (0 vs 1).

The investigators identified the 4-month progression-free survival rate with nanoliposomal irinotecan plus fluorouracil and leucovorin as the primary endpoint. Progression-free survival, objective response rate, overall survival, and safety parameters were evaluated as secondary endpoints. Follow-up data were provided for a median of 13.5 months.

Survival and Disease Progression

The primary endpoint was met, with 51.0% of the patients who received nanoliposomal irinotecan plus fluorouracil and leucovorin experiencing nonprogressive disease at 4 months; in those treated with gemcitabine plus cisplatin, the rate was 59.5%. The median duration of progression-free survival was 6.0 months with nonplatinum chemotherapy and 6.9 months with the standard regimen (hazard ratio [HR] = 0.85; P = .52). The median durations of overall survival were 15.7 13.6 months, respectively (HR = 0.94; P = .78).

An exploratory comparison revealed a numerical but statistically insignificant benefit with nanoliposomal irinotecan plus fluorouracil and leucovorin vs gemcitabine plus cisplatin (HR for progression-free survival = 0.85; HR for overall survival = 0.94). Based on an analysis for stratification parameters, no differences were identified for sex and ECOG performance status score; however, they were found for tumor localization. The objective response rate was higher with nonplatinum chemotherapy vs the standard regimen (24.5% vs 11.9%).

Adverse Events

The safety profiles of both therapies appeared to be consistent with previous findings, and no unexpected toxicities were documented. Patients treated with nanoliposomal irinotecan plus fluorouracil and leucovorin experienced more gastrointestinal toxicities, including grade 3 to 4 diarrhea (22.4%), nausea (12.2%), and mucositis (2.0%). Treatment with gemcitabine plus cisplatin was associated with more hematologic toxicities, namely grade 3 to 4 neutropenia (21.9%) and anemia (26.8%). No grade 5 toxicities were reported.

“To our knowledge, NIFE is the first prospective trial demonstrating efficacy of nanoliposomal irinotecan plus fluorouracil and leucovorin in the first-line therapy setting of advanced cholangiocarcinoma,” the investigators concluded. “This regimen merits further validation in a larger phase III trial.” 

Lukas Perkhofer, MD, of the University of Ulm, Germany, is the corresponding author of the Journal of Clinical Oncology article. 

Disclosure: The study was funded by Servier. For full disclosures of the study authors, visit ascopubs.org.