On February 13, the U.S. Food and Drug Administration (FDA) approved irinotecan liposome (Onivyde) with oxaliplatin, fluorouracil, and leucovorin for the first-line treatment of metastatic pancreatic adenocarcinoma. The efficacy of the triplet was evaluated in NAPOLI-3 (ClinicalTrials.gov identifier NCT04083235), a randomized, multicenter, open-label, active-controlled trial in 770 patients with metastatic pancreatic adenocarcinoma who had not previously received chemotherapy in the metastatic setting. Random assignment was stratified by region, liver metastases, and Eastern Cooperative Oncology Group performance status. Patients were randomly assigned 1:1 to receive either:

• Irinotecan liposome at 50 mg/m² as an intravenous infusion over 90 minutes, followed by oxaliplatin at 60 mg/m²as an intravenous infusion over 120 minutes, followed by leucovorin at 400 mg/m² intravenously over 30 minutes, followed by fluorouracil at 2,400 mg/m² intravenously over 46 hours, every 2 weeks (NALIRIFOX arm)
• Nab-paclitaxel at 125 mg/m²as an intravenous infusion over 35 minutes, followed by gemcitabine at 1,000 mg/m² intravenously over 30 minutes on days 1, 8, and 15 of each 28-day cycle (gemcitabine plus nab-paclitaxel arm).

There was a statistically significant improvement in overall and progression-free survival for patients in the NALIRIFOX arm over the gemcitabine plus nab-paclitaxel arm. Median overall survival was 11.1 months (95% confidence interval [CI] = 10.0–12.1 months) in the NALIRIFOX arm and 9.2 months (95% CI = 8.3–10.6 months) in the gemcitabine plus nab-paclitaxel arm (hazard ratio [HR] = 0.84, 95% CI = 0.71–0.99, P = .0403). Median progression-free survival was 7.4 months (95% CI = 6.0–7.7 months) in the NALIRIFOX arm and 5.6 months (95% CI = 5.3–5.8 months) in the gemcitabine plus nab-paclitaxel arm (HR = 0.70, 95% CI = 0.59–0.85, P = .0001). Objective response rates were 41.8% (95% CI = 36.8%–46.9%) and 36.2% (95% CI = 31.4%–41.2%), respectively. The recommended irinotecan liposome dose is 50 mg/m² administered by intravenous infusion over 90 minutes every 2 weeks. Irinotecan liposome should be administered prior to oxaliplatin, fluorouracil, and leucovorin. There is no recommended dosage of irinotecan liposome for patients with serum bilirubin above the upper limit of normal. The application was granted Orphan Drug designation.