58P - Efficacy and safety of liposomal irinotecan (nal-IRI) plus fluorouracil (5-FU) and leucovorin (LV) versus 5-FU/LV alone for advanced biliary tract cancer (BTC) after progression on gemcitabine-based therapy: A pooled analysis of the NIFTY and NALIRICC trials

Background

Nal-IRI combined with 5-FU/LV has been explored as a second-line treatment for BTC following progression on gemcitabine-based therapy in the randomized Korean NIFTY and German NALIRICC trials. Despite their similar designs, these studies reported conflicting outcomes, necessitating a comprehensive pooled analysis to evaluate the efficacy and safety of this combination.

Methods

Individual patient-level data were pooled from the ITT populations of the NIFTY and NALIRICC trials. Patients received nal-IRI (70 mg/m²) D1 plus LV (400 mg/m²) D1 and 5-FU (2400 mg/m²) D1-2, or 5-FU/LV alone, every 2 weeks. The primary endpoint was progression-free survival (PFS), and secondary endpoints included overall survival (OS), overall response rates (ORR), and safety profile.

Results

A total of 278 patients were included with 137 in the nal-IRI plus 5-FU/LV group and 141 in the 5-FU/LV group. Baseline characteristics were well balanced between two groups, with the majority (95%) previously treated with gemcitabine plus cisplatin. The nal-IRI plus 5-FU/LV group showed significantly longer median PFS (3.6 mo [95% CI, 2.7-4.4] vs 1.8 mo (95% CI, 1.5-2.6), HR 0.65 [95% CI, 0.51-0.84], p<0.001) and a trend toward improved median OS (8.1 mo [95% CI, 6.0-8.9] vs 6.1 mo [95% CI, 5.3-7.5], HR 0.77 [95% CI, 0.59-1.00], p=0.051). ORR was also higher in the nal-IRI plus 5-FU/LV group (17.5% vs 2.8%) than the 5-FU/LV group (p<0.001). Notably, adverse events varied by ethnicity, with gastrointestinal toxicities and neutropenia more common in Caucasian and Asian cohorts, respectively. There were different patterns of dose modification between Caucasian and Asian cohorts; dose reduction occurred in 33.3% vs 67.0%; and treatment discontinuation without disease progression in 31.3% vs 8.0%, respectively.

Conclusions

Nal-IRI combined with 5-FU/LV significantly improved PFS and ORR in patients who progressed after gemcitabine-based therapy, indicating its potential as a standard second-line treatment. Differences in safety profiles across ethnicities underscore the need for tailored treatment approaches.

Clinical trial identification

NCT03542508, NCT03464968.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Servier.

Disclosure

C. Yoo: Financial Interests, Personal, Invited Speaker: Bayer, Celgene, Eisai, Ipsen, Servier, Roche, Novartis; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Research Grant: AstraZeneca, Bayer, Servier; Financial Interests, Institutional, Research Grant: Genentech. A. Vogel: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Boehringer Mannheim, Eisai, Incyte, Ipsen, Janssen, MSD, Pierre Fabre, Roche, Servier, Tyra, Tahio; Financial Interests, Personal, Invited Speaker: BMS, Eisai, Ipsen, Lilly, MSD, Roche, AstraZeneca; Financial Interests, Personal, Steering Committee Member: Roche, MSD, BeiGene, Jiangsu Hengrui Medicines. All other authors have declared no conflicts of interest.