Results of the NIFTY trial demonstrated that liposomal irinotecan plus 5-fluorouracil and leucovorin significantly improved efficacy outcomes compared with 5-fluorouracil plus leucovorin alone in patients with biliary tract cancer who progressed on prior gemcitabine/cisplatin, with a manageable adverse event profile.
NIFTY is an investigator-initiated, multicenter, open-label, randomized, phase 2b study (ClinicalTrials.gov Identifier: NCT03524508) that evaluated liposomal irinotecan in combination with 5-fluorouracil and leucovorin (nal-IRI plus 5-FU/LV) versus 5-FU/LV alone in patients with metastatic biliary tract cancer (BTC) after progression on gemcitabine/cisplatin. Results of the NIFTY trial were presented at the 2021 American Society of Clinical Oncology Annual Meeting.
Eligibility criteria included age >19 years, Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1, histologically or cytologically confirmed metastatic BTC, disease progression on first-line gemcitabine/cisplatin, and no prior second-line chemotherapy. Eligible patients were randomized in a 1:1 ratio to receive nal-IRI (70 mg/m2, 90 minutes) plus 5-FU (2400 mg/m2, 46 hours)/LV (400 mg/m2, 30 minutes) every 2 weeks until disease progression or intolerable toxicities or 5-FU/LV alone. Stratification was based on primary tumor site (intrahepatic, extrahepatic, gallbladder), prior surgery, and participating center. Tumor response was evaluated every 6 weeks on a fixed schedule. The primary end point was blinded independent central review (BICR)-assessed progression-free survival (PFS) rate per RECIST version 1.1. Secondary end points included investigator-assessed PFS, overall survival (OS), overall response rate (ORR) per RECIST version 1.1, safety profile, and quality of life. This study was designed to have 80% power, with a 2-sided type I error of 5% to detect a hazard ratio (HR) of 0.6 (P1: median 3.3 months) for PFS with the addition of naI-IRI to 5-FU/LV (P0: median 2 months). With an expected 10% loss to follow-up, a total of 174 patients were required (ie, 87 in each treatment group).
Overall, 174 patients received study treatment and comprised the full analysis set; of these, 88 patients received nal-IRI plus 5-FU/LV and 86 received 5-FU/LV alone. The baseline characteristics of the 2 groups were well-balanced. The median participant age was 64 years, and the majority of the patients were male (n = 99). Overall, 74 patients had intrahepatic cholangiocarcinoma, 47 had extrahepatic cholangiocarcinoma, and 53 had gallbladder cancer.
With a median follow-up of 11.8 months, median PFS per BICR was significantly prolonged in the nal-IRI-plus-5-FU/LV group compared with the 5-FU/LV-alone group (7.1 months vs 1.4 months, respectively; HR, 0.56; 95% confidence interval [CI], 0.39-0.81; P = .0019). Similar PFS prolongation was achieved per investigator review (median PFS, 3.9 months vs 1.6 months, respectively; HR, 0.48; 95% CI, 0.34-0.69; P <.0001). The PFS advantage translated to significant improvement in OS with nal-IRI-plus-5-FU/LV therapy (median OS, 8.6 months vs 5.5 months, respectively; HR, 0.68; 95% CI, 0.48-0.98; P = .0349). Consistently, ORR was significantly higher in the nal-IRI-plus-5-FU/LV arm versus the 5-FU/LV-alone arm, both per BICR (14.8% vs 5.8%, respectively; P = .0684) and per investigator review (19.3% vs 2.3%, respectively; P = .0002).
Grade ≥3 adverse events (AEs) were higher in the nal-IRI-plus-5-FU/LV group than in the 5-FU/LV-alone group (77.3% vs 33.7%). The most common grade ≥3 AEs in the nal-IRI-plus-5-FU/LV group were neutropenia (23.9%), fatigue (12.5%), and nausea (5.7%).
Based on the results of the NIFTY trial, the investigators concluded that nal-IRI plus 5-FU/LV significantly improved efficacy outcomes compared with 5-FU/LV alone in patients with BTC who had progressed on prior gemcitabine/cisplatin, with a manageable AE profile.
Source: Yoo C, Kim KP, Kim I, et al. Liposomal irinotecan (nal-IRI) in combination with fluorouracil (5-FU) and leucovorin (LV) for patients with metastatic biliary tract cancer (BTC) after progression on gemcitabine plus cisplatin (GemCis): multicenter comparative randomized phase 2b study (NIFTY). J Clin Oncol. 2021;39(suppl_15):4006-4006.
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