Abstract 55P
Background
The NIFTY trial showed that nal-IRI plus 5-FU/LV significantly improved the blinded-independent central review (BICR)- and investigator-assessed progression-free survival (PFS) and overall survival (OS) compared with 5-FU/LV. An updated analysis (data cutoff: 31 DEC 2021) was performed to assess the long-term efficacy outcomes (extension follow-up of 1.3 years). As there was a concern about the large discrepancy rates (30%) between BICR and investigator review in the previous analysis, BICR was performed again by three independent radiologists with more experience in clinical trials and also through external monitoring.
Methods
Pts with > 19 yrs, ECOG PS 0-1, metastatic BTC, and disease progression on prior GemCis were eligible. Pts were randomized 1:1 to nal-IRI plus 5-FU/LV or 5-FU/LV, every 2 weeks. Tumor response was evaluated per RECIST v1.1, every 6 wks.
Results
Between SEP 2018 and FEB 2020, 88 and 86 pts were included in nal-IRI plus 5-FU/LV and 5-FU/LV groups, respectively. With median follow-up of 6.1 mo (IQR 3.5-12.6), median PFS per BICR in nal-IRI plus 5-FU/LV group and 5-FU/LV group was 3.9 mo (95% CI, 2.6-4.7) and 1.5 mo (1.2-1.9), respectively (HR=0.38 [0.26-0.54], p<0.0001); median PFS per investigator review was 3.9 mo (2.7-5.2) and 1.6 mo (1.3-2.2), respectively (HR=0.51 [0.36-0.71], p<0.0001). Median OS was 8.6 mo (5.4-10.5) and 5.3 mo (4.7-7.2), respectively (HR=0.68 [0.48-0.95], p=0.024). ORR was 12.5% and 3.5% per BICR, respectively (p=0.043) and 19.3% and 2.3% per investigator review, respectively (p=0.0002). The discordance rate for tumor progression date between BICR and investigators was 10.7%. In multivariate analyses for prognostic factors, bone mets was associated with poor PFS; male, CA 19-9 > median, elevated CRP, and albumin > median were associated with poor OS; prior GemCis duration > median was associated with better OS.
Conclusions
The survival benefits of 2nd line nal-IRI plus 5-FU/LV versus 5-FU/LV were maintained over an extended follow-up in BTC pts.
Clinical trial identification
NCT03524508 Release date: May 14, 2018.
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Servier and HK Inno.N.
Disclosure
C. Yoo: Financial Interests, Personal, Invited Speaker: Bayer, Celgene, Eisai, Ipsen, Servier, Roche; Financial Interests, Personal, Advisory Board: AstraZeneca. G.K. Abou-Alfa: Financial Interests, Personal, Advisory Board: Adicet, Alnylam, AstraZeneca, Autem, Beigene, Berry Genomics, Boehringer Ingelheim, Celgene, Cend, CytomX, Eisai, Eli Lilly, Exelixis, Flatiron, Genentech/Roche, Genoscience, Helio, Helsinn, Incyte, Ipsen, Merck, Nerviano, Newbridge, Novartis, QED, Redhill, Rafael, Servier, Silenseed, Sobi, Vector, Yiviva; Financial Interests, Personal, Other, IP License: PCT/US2014/031545 filed on March 24, 2014, and priority application Serial No.: 61/804,907; Filed: March 25, 2013; Financial Interests, Institutional, Research Grant: Arcus, AstraZeneca, BioNtech, BMS, Celgene, Flatiron, Genentech/Roche, Genoscience, Incyte, Polaris, Puma, QED, Silenseed, Yiviva; Non-Financial Interests, Principal Investigator: AstraZeneca, Yiviva, QED. All other authors have declared no conflicts of interest.