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.
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.
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.
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.
Legal entity responsible for the study
Servier and HK Inno.N.
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.