In a Korean phase IIb trial (NIFTY) reported in The Lancet Oncology, Yoo et al found that the addition of liposomal irinotecan to fluorouracil/leucovorin improved progression-free survival as a second-line treatment for patients with metastatic biliary tract cancer whose disease had progressed on gemcitabine/cisplatin.

Study Details

In the multicenter open-label trial, 174 patients were randomly assigned between September 2018 and February 2020 to receive liposomal irinotecan plus fluorouracil and leucovorin (n = 88) or fluorouracil and leucovorin alone (n = 86). Treatment consisted of liposomal irinotecan at 70 mg/m², leucovorin at 400 mg/m², and fluorouracil at 2,400 mg/m² over 46 hours every 2 weeks or leucovorin/fluorouracil only every 2 weeks, with treatment continued until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival on blinded independent central review.

Progression-Free Survival

Median follow-up was 11.8 months (interquartile range = 7.7–18.7 months). Median progression-free survival was 7.1 months (95% confidence interval [CI] = 3.6–8.8 months) in the liposomal irinotecan group vs 1.4 months (95% CI = 1.2–1.5 months) in the control group (hazard ratio [HR] = 0.56, 95% CI = 0.39–0.81, P = .0019). Rates at 6 months were 55.7% vs 26.2%.

Objective responses (all partial) were observed in 14.8% vs 5.8% of patients (P = .068). Disease control rates were 64.8% vs 34.9% (P = .0002).

Subsequent systemic therapy was received by 35% vs 32% of patients, most commonly fluoropyrimidine plus cisplatin or oxaliplatin (17% vs 11%). Median overall survival was 8.6 months (95% CI = 5.4–10.5 months) in the liposomal irinotecan group vs 5.5 months (95% CI = 4.7–7.2 months) in the control group (HR = 0.68, 95% CI = 0.48–0.98, P = .035); rates at 6 months were 60.7% vs 45.9%.

Adverse Events

The most common grade 3 or 4 adverse events in the liposomal irinotecan group were neutropenia (24% vs 1% in control group) and fatigue/asthenia (13% vs 3%). Serious adverse events occurred in 42% vs 24% and were considered related to treatment in 7% vs 1%. Adverse events led to discontinuation of treatment in 7% vs 3% of patients, and led to death in 6% vs 1%, with none of the deaths considered related to treatment.

The investigators concluded, “Adding liposomal irinotecan to fluorouracil and leucovorin significantly improved blinded independent central review–assessed progression-free survival in patients with advanced biliary tract cancer. Liposomal irinotecan plus fluorouracil and leucovorin could be considered a standard-of-care second-line therapy for advanced biliary tract cancer.”

Changhoon Yoo, MD, of Asan Medical Center, University of Ulsan College of Medicine, Seoul, is the corresponding author for The Lancet Oncology article.

Disclosure: The study was funded by Servier and HK inno.N. For full disclosures of the study authors, visit thelancet.com.