Therapeutic options in pre-treated advanced biliary tract cancer (BTC) are limited. Although the ABC-06 trial demonstrated clinical benefit for mFOLFOX, there is an unmet need for more effective 2nd line therapies. The aim of this study was to evaluate the efficacy of pegylated liposomal irinotecan formulation (nal-IRI)/5-FU/leucovorin (LV) compared to 5-FU/LV in 2nd line BTC.
NALIRICC is a prospective, randomized, two-sided, phase II study. Pts > 18 years, with ECOG PS 0/1, histologically confirmed metastatic BTC and progression on 1st line Gemcitabine-based therapy were eligible. Trial interventions were Arm A nal-IRI (80 mg/m2) plus 5-FU (2400 mg/m2)/LV (400 mg/m2), q2w or Arm B 5-FU/LV, q2w. Pts were stratified according to primary tumor site, and response was evaluated per RECIST v1.1, every 6 weeks. Primary endpoint (EP) was progression-free survival (PFS). Secondary EPs were overall survival (OS), overall response rates (ORR), safety and QoL (EORTC QLQ C30). This study was designed to improve median PFS from 1.5 months (P0) to 3 months (P1; HR 0.5) with 2-sided α of 0.05, power of 90.3%; 99 pts required in total.
In total 100 pts were randomized in 17 German centers (49 pts: nal-IRI/5-FU/LV arm/ 51 pts: 5-FU/LV arm). 64/19/17 pts had intra-/extrahepatic/gallbladder cancers. Pt characteristics were well balanced between the two arms. Trial results see the table. Most common grade ≥3 Adverse Events in nal-IRI/5-FU/LV group were decreased neutrophil counts (16.6%), diarrhea (14.6%), and nausea (8.3%). 27.5% of patients in the 5-FU/LV groups received irinotecan-based therapies post-progression. QoL was similar between both arms. Table: 53MO
NALIRICC-Trial results, median follow-up of 5,9 months
|Treament arm||ORR [%]||mOS [months]||mPFS [months]||AEs ≥ 3 in % of pts|
|Arm A, Nal-IRI and 5-FU/LV, n=49||14.3||6.9||2.76||70.8|
|Arm B, 5-FU/LV, n=51||3.9||8.21||2.3||50|
The NALIRICC-trial did not meet its primary EP. The addition of nal-IRI to 5-FU/LV did not improve PFS or OS compared to 5-FU/LV alone and was associated with higher toxicity. 5FU/LV may be considered as a reasonable alternative in 2nd line advanced BTC.
Clinical trial identification
Legal entity responsible for the study
AIO-Studien-gGmbH supported by Servier.
A. Vogel: Financial Interests, Personal, Invited Speaker: Roche, BMS, MSD, Novartis, Eisai, Ipsen, Incyte, PierreFabre, Lilly, Imaging Equipment Ltd (AAA), Roche, MSD, Beigene, Jiangsu Hengrui Medicines.; Financial Interests, Personal, Advisory Board: Roche, Bayer, BMS, MSD, Eisai, Ipsen, Incyte, PierreFabre, Lilly, AstraZeneca, Boston Scientific, Sirtex, Daiichi-Sankyo. G. Folprecht: Financial Interests, Personal, Invited Speaker: Roche / Genentech, Falk Foundation, Lilly; Financial Interests, Personal, Advisory Board: Sanofi-Aventis, Merck, BMS, MSD, Servier, Pierre Fabre, Roche / Genentech, Bayer, Exact Sciences. A. Kretzschmar: Financial Interests, Personal, Advisory Role: Servier, Roche, BMS, MSD, Merck, Sanofi. N. Ziegenhagen: Financial Interests, Institutional, Sponsor/Funding, Clinical Trial: Pfizer, Boehringer Ingelheim, MSD Sharp & Dohme GmbH, Astellas Pharma, Amgen; Non-Financial Interests, Institutional, Member, Membership: ESMO. S. Boeck: Financial Interests, Personal, Project Lead: Incyte; Financial Interests, Institutional, Sponsor/Funding, Clinical Trial: Servier. D. Pink: Financial Interests, Institutional, Invited Speaker: Blueprint, PharmaMar, BMS, EUSA-Pharma, PharmaMar, Lilly, Roche; Financial Interests, Institutional, Advisory Board: Roche, PharmaMar, Boehringer Ingelheim; Financial Interests, Institutional, Other, scientific lead of a trial with funding from Novartis: Novartis; Non-Financial Interests, Member: ASCO, Deutsche Krebsgesellschaft - German Cancer Society (DKG), Connective Tissue Oncology Society (CTOS), Deutsche Sarkomstiftung (DSS). T.O. Götze: Financial Interests, Personal, Advisory Role: Amgen, AstraZeneca, Bayer, BMS, Daiichi Sankyo, Foundation Medicine, Lilly, MCI, MSD Sharp Dohme, Novartis, Roche, Sanofi, Aventis, Servier; Financial Interests, Personal, Project Lead: Lilly, AstraZeneca, Incyte, DGF German Research Foundation, GBA Gemeinsamer Bundesausschuss, Deutsche Krebshilfe. E. Goekkurt: Financial Interests, Institutional, Advisory Board: BMS, Daiichi Sankyo, MSD; Financial Interests, Institutional, Principal Investigator, local PI: AstraZeneca, BMS, Daiichi Sankyo, MSD, Novartis. U. Graeven: Financial Interests, Personal, Stocks/Shares: Biontech; Financial Interests, Personal, Advisory Role, Honoraria: Boehringer Ingelheim, Amgen, AstraZeneca, BMS, MSD Oncology, Sanofi Aventis, Fujifilm, Novartis; Financial Interests, Personal, Other, Travelexpenses: Merck KGaA, Amgen, Boehringer Ingelheim, GSK. A. Saborowski: Financial Interests, Personal, Advisory Role: Roche, BMS, Falk Foundation, Servier. All other authors have declared no conflicts of interest.