FDA Approves Irinotecan Liposome for First-Line Metastatic Pancreatic Adenocarcinoma

On February 13, 2024, the US Food and Drug Association (FDA) has granted approval to irinotecan liposome with oxaliplatin, fluorouracil, and leucovorin for the treatment of patients with metastatic pancreatic adenocarcinoma in the first-line setting.

This regulatory decision was based upon results from the multicenter, open-label phase 3NAPOLI 3 trial. In NAPOLI 3, 770 patients with metastatic pancreatic adenocarcinoma who had not previously been treated with chemotherapy in the metastatic setting. Patients were randomized on a 1-to-1 basis to receive either 50 mg/m² irinotecan liposome followed by oxaliplatin, leucovorin, and fluorouracil (NALIRIFOX), or nab-paclitaxel plus gemcitabine (Gem-NabP). The main outcome was overall survival (OS) with additional outcomes including progression-free survival (PFS) and objective response rate (ORR).

There was a statistically significant improvement in both OS and PFS seen in the NALIRIFOX arm compared with the Gem-NabP arm. The median OS was 11.1 months in the NALIRIFOX arm vs 9.2 months in the Gem-NabP arm (hazard ratio [HR], 0.84; 95% confidence interval [CI], 0.71 to 0.99; P = .0403). The median PFS was 7.4 months in the NALIRIFOX arm vs 5.6 months in the Gem-NabP arm (HR, 0.70; 95% CI, 0.59 to 0.85, P = .0001). The ORR was 41.8% in the NALIRIFOX arm vs 36.2% in the Gem-NabP arm.

The most common adverse events associated with NALIRIFOX as seen in ≥20% of patients, with a difference of ≥5% for all grades, or of ≥2% for grades 3/4 when compared with the Gem-NabP arm, were diarrhea, fatigue, nausea, vomiting, decreased appetite, abdominal pain, mucosal inflammation, constipation, and decreased weight. The most common laboratory abnormalities, in ≥10% of patients as grade 3/4, were decreased neutrophils, decreased potassium, decreased lymphocyte, and decreased hemoglobin.

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

Source:

FDA approves irinotecan liposome for first-line treatment of metastatic pancreatic adenocarcinoma. Published February 13, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-irinotecan-liposome-first-line-treatment-metastatic-pancreatic-adenocarcinoma