Liposomal irinotecan plus fluorouracil and leucovorin versus fluorouracil and leucovorin for metastatic biliary tract cancer after progression on gemcitabine plus cisplatin (NIFTY): a multicentre, open-label, randomised, phase 2b study
Mené sur 174 patients atteints d'un cancer des voies biliaires de stade métastatique, cet essai multicentrique de phase IIB évalue l'efficacité, du point de vue de la survie sans progression, et la toxicité de l'ajout de l'irinotécan sous forme liposomale à un traitement de seconde ligne combinant fluorouracile et leucovorine, après l'échec d'un traitement à base de gemcitabine et cisplatine
Background : The prognosis of patients with advanced biliary tract cancer who have progressed ongemcitabine plus cisplatin is dismal. We aimed to investigate the efficacy and safety of second-line liposomal irinotecan plus fluorouracil and leucovorin in patients with metastatic biliary tract cancer that has progressed on gemcitabine plus cisplatin. Methods : This multicentre, open-label, randomised, phase 2b (NIFTY) study was done at fiveacademic institutions in South Korea and included patients aged 19 years or olderwith histologically or cytologically confirmed metastatic biliary tract cancer thathad progressed on first-line gemcitabine plus cisplatin and an Eastern CooperativeOncology Group performance status of 0 or 1. By use of an interactive web-based responsesystem integrated with an electronic data capture system, patients were randomly assigned(1:1) using permuted blocks (block size 4) to receive either intravenous liposomalirinotecan (70 mg/m2 for 90 min) plus intravenous leucovorin (400 mg/m2 for 30 min) and intravenous fluorouracil (2400 mg/m2 for 46 h) every 2 weeks or leucovorin and fluorouracil only every 2 weeks, and werestratified by primary tumour site, previous surgery with curative intent, and participatingcentre. Study treatment was continued until the patient had disease progression orunacceptable toxicities, or withdrew consent. The primary endpoint was blinded independentcentral review (BICR)-assessed progression-free survival. The primary endpoint andsafety were assessed in the full analysis set and the safety analysis set, respectively,both of which comprised all randomly assigned patients who received at least one doseof the study treatment. This trial is registered with ClinicalTrials.gov, NCT03524508, and enrolment is complete. Findings : Between Sept 5, 2018, and Feb 18, 2020, 193 patients were screened for eligibility,of whom 174 (88 in the liposomal irinotecan plus fluorouracil and leucovorin groupand 86 in the fluorouracil plus leucovorin group) were enrolled and included in thefull analysis and safety analysis sets. At a median follow-up of 11·8 months (IQR7·7–18·7), the median BICR-assessed progression-free survival was significantly longerin the liposomal irinotecan plus fluorouracil and leucovorin group (7·1 months, 95%CI 3·6–8·8) than in the fluorouracil and leucovorin group (1·4 months, 1·2–1·5; hazardratio 0·56, 95% CI 0·39–0·81; p=0·0019). The most common grade 3–4 adverse eventswere neutropenia (21 [24%] of 88 in the liposomal irinotecan plus fluorouracil andleucovorin group vs one [1%] of 86 in the fluorouracil and leucovorin group) and fatigue or asthenia(11 [13%] vs three [3%]). Serious adverse events occurred in 37 (42%) patients receiving liposomalirinotecan plus fluorouracil and leucovorin and 21 (24%) patients receiving fluorouraciland leucovorin. There were no treatment-related deaths. Interpretation : Adding liposomal irinotecan to fluorouracil and leucovorin significantly improvedBICR-assessed progression-free survival in patients with advanced biliary tract cancer.Liposomal irinotecan plus fluorouracil and leucovorin could be considered a standard-of-caresecond-line therapy for advanced biliary tract cancer.
The Lancet Oncology , 2021