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

Background

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 1^st-line treatment option in advanced BTC.

Methods

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.

Results

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: LBA10

ICCA: intrahepatic CCA, ECCA: Extrahepatic CCA, NE: not estimable

Conclusions

In the phase II NIFE trial nal-IRI/5-FU/LV showed efficacy as 1^st-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.

Clinical trial identification

AIO-YMO HEP-0315 (NIFE); EudraCT 2016-002467-34; NCT03044587.

Editorial acknowledgement

Legal entity responsible for the study

AIO-Studien GmbH.

Funding

Servier.

Disclosure

M. Sinn: Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Incyte; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Servier; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Sanofi. T.O. Goetze: Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Advisory Board: MSD Sharp Dohme; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: Celgene; Financial Interests, Personal, Advisory Board: Servier; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Ipsen; Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Personal, Invited Speaker: MCI; Financial Interests, Personal, Invited Speaker: MSD Sharp Dohme; Financial Interests, Personal, Research Grant: AstraZeneca; Financial Interests, Personal, Research Grant: Incyte; Financial Interests, Personal, Research Grant: Lilly. D. Waldschmidt: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Celgene; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Advisory Board: Incyte; Financial Interests, Personal, Advisory Board: Ipsen; Financial Interests, Personal, Advisory Board: Falk; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Servier; Financial Interests, Personal, Advisory Board: Shire Baxalta; Financial Interests, Personal, Advisory Board: Sirtex. T. Seufferlein: Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Advisory Board: Pierre Fabre; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Baxalta; Financial Interests, Personal, Advisory Board: Servier; Financial Interests, Personal, Speaker’s Bureau: Sanofi; Financial Interests, Personal, Speaker’s Bureau: Pierre Fabre; Financial Interests, Personal, Speaker’s Bureau: Pfizer; Financial Interests, Personal, Speaker’s Bureau: Baxalta; Financial Interests, Personal, Speaker’s Bureau: Servier; Financial Interests, Personal, Research Grant: Boehringer; Financial Interests, Personal, Research Grant: Sanofi; Financial Interests, Personal, Research Grant: Celgene; Financial Interests, Personal, Research Grant: Amgen. T.J. Ettrich: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Ipsen; Financial Interests, Personal, Invited Speaker: Ipsen; Financial Interests, Personal, Advisory Board: Sanofi Aventis; Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal, Advisory Board: Pierre-Fabre Pharma; Financial Interests, Personal, Advisory Board: Incyte; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Institutional, Research Grant: Servier; Financial Interests, Institutional, Research Grant: Sanofi Aventis; Financial Interests, Institutional, Research Grant: Celgene. All other authors have declared no conflicts of interest.