FDA Approves Irinotecan Liposome as First-Line Treatment of Metastatic Pancreatic Adenocarcinoma

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.

NAPOLI-3

Efficacy 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 one of the following treatments:

• NALIRIFOX: Irinotecan liposome at 50 mg/m² as an intravenous infusion over 90 minutes, followed by oxaliplatin at 60 mg/m² as 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.
• Gem+NabP: Nab-paclitaxel at 125 mg/m² as 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.

The main efficacy outcome measure was overall survival; additional efficacy measures were investigator-assessed progression-free survival and objective response rate. NAPOLI-3 demonstrated a statistically significant improvement in overall and progression-free survival for patients in the NALIRIFOX arm over the Gem+NabP 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 Gem+NabP 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 Gem+NabP arm (HR = 0.70, 95% CI = 0.59–0.85, P = .0001). Objective response rate was 41.8% (95% CI = 36.8%–46.9%) in the NALIRIFOX arm and 36.2% (95% CI = 31.4%–41.2%) in the Gem+NabP arm.

The most common adverse reactions of NALIRIFOX (≥ 20%, with a difference between arms of ≥ 5% for all grades or ≥ 2% for grades 3 or 4 compared to Gem+NabP) were diarrhea, fatigue, nausea, vomiting, decreased appetite, abdominal pain, mucosal inflammation, constipation, and decreased weight. The most common laboratory abnormalities (≥ 10% grade 3 or 4) were decreased neutrophils, decreased potassium, decreased lymphocyte, and decreased hemoglobin.

The recommended irinotecan liposome dose is 50 mg/m² administered by intravenous infusion over 90 minutes every 2 weeks. Administer irinotecan liposome before oxaliplatin, fluorouracil, and leucovorin. There is no recommended dosage of irinotecan liposome for patients with serum bilirubin above the upper limit of normal.

This application was granted Orphan Drug designation.