LBA10 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

Survival and treatment options in advanced biliary tract cancer (BTC) are limited with the current standard of care gemcitabine/cisplatin. The NIFE study examined nanoliposomal-irinotecan (nal-IRI)/5-FU/leucovorin (LV) as an alternative 1st-line treatment option in advanced BTC. NIFE is a prospective, randomized, two-sided, phase II study. Advanced BTC patients 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), sex and ECOG (0 vs. 1). Arm A was planned as a Simon's optimal two-stage design and arm B served as an internal control for selection bias. As primary endpoint a 4 months (mo) progression free survival (PFS) rate ≥50% in the ITT-population was defined. Between 01/2018-09/2020 93 patients were randomly assigned in 21 German centers. Two patients violating inclusion criteria had to be excluded from the ITT population (n=91) due to inappropriate randomization. The NIFE trial met its primary endpoint with a PFS-rate of 51% at 4mo in the ITT population (arm A). Median PFS in arm A was 5.98mo (2.37-9.59) and in arm B 6.87mo (2.46-7.82). Provisional median overall survival (mOS) was 15.9mo (10.58-21.85) in arm A and 13.63mo (6.51-17.68) in arm B with ongoing follow-up at data closesure. Median PFS in intrahepatic (ICCA) vs. extrahepatic (ECCA) cholangiocarcinoma was 3.45mo (2.10-6.05) vs. 9.59mo (1.94-15.67) in arm A and 7.72mo (6.05-9.46) vs. 1.76mo (0.16-6.87) in arm B. Corresponding mOS times were ICCA 14.19/ECCA 18.23mo in arm A and ICCA 16.36/ECCA 6.34mo in arm B.Table: LBA10ITT (n=91)Arm A (n=49) Nal-IRI/5-FU/LVArm B (n=42) Gemcitabine/cisplatinPFS rate at 4mo51.0% ICCA (n=34) 41.2% ECCA (n=15) 73.3%59.5% ICCA (n=32) 71.9% ECCA (n=10) 20.0%mPFS5.98mo (95% CI 2.37-9.59) ICCA (n=34) 3.45mo (95% CI 2.10-6.05) ECCA (n=15) 9.59mo (95% CI 1.94-15.67)6.87mo (95% CI 2.46-7.82) ICCA (n=32) 7.72mo (95% CI 6.05-9.46) ECCA (n=10) 1.76mo (95% CI 0.16-6.87)mOS15.9mo (95% CI 10.58-21.85) ICCA (n=34) 14.19mo (95% CI 7.69-21.85) ECCA (n=15) 18.23mo (95% CI 8.67-30.95)13.63mo (95% CI 6.51-17.68) ICCA (n=32) 16.36mo (95% CI 7.46-19.91) ECCA (n=10) 6.34mo (95% CI 0.16-NE)ORR24.5%11.9%DCR at 2mo57.1%57.1%ICCA: intrahepatic CCA, ECCA: Extrahepatic CCA, NE: not estimable Open table in a new tab ICCA: intrahepatic CCA, ECCA: Extrahepatic CCA, NE: not estimable In the phase II NIFE trial nal-IRI/5-FU/LV showed efficacy as 1st-line treatment of advanced BTC with no new safety findings. ECCA and ICCA responded differently to drug interventions, with a clear benefit for nal-IRI/5-FU/LV in ECCA.