FDA Alert

FDA Approves Irinotecan Liposome For First-Line Treatment of Patients With Metastatic Pancreatic Adenocarcinoma

Anthony Calabro, MA

On February 13, the FDA approved irinotecan liposome with oxaliplatin, fluorouracil, and leucovorin (also known as NALIRIFOX) as a first-line regimen for the management of patients with metastatic pancreatic adenocarcinoma.

The approval was based on results from the NAPOLI 3 study, a randomized, multicenter, open-label, active-controlled trial that included 770 patients with metastatic pancreatic adenocarcinoma who had not previously received chemotherapy in the metastatic setting. Patients were randomly assigned (1:1) to receive either NALIRIFOX or nab-paclitaxel plus gemcitabine (Gem+NabP).

Patients randomly assigned to the NALIRIFOX arm received irinotecan liposome 50 mg/m2 as an intravenous infusion over 90 minutes, followed by oxaliplatin 60 mg/m2 as an intravenous infusion over 120 minutes, followed by leucovorin 400 mg/m2 intravenously over 30 minutes, followed by fluorouracil 2400 mg/m2 intravenously over 46 hours, every 2 weeks.

Participants in the Gem+NabP group, received nab-paclitaxel 125 mg/m2 as an intravenous infusion over 35 minutes, followed by gemcitabine 1000 mg/m2 intravenously over 30 minutes on days 1, 8, and 15 of each 28-day cycle.

Overall survival (OS) was the main efficacy outcome in this study, with investigator-assessed progression-free survival (PFS) and objective response rate (ORR) as secondary efficacy outcomes.

In the NAPOLI 3 study, the NALIRIFOX group demonstrated a statistically significant improvement in OS and PFS compared with the Gem+NabP arm. Median OS was 11.1 months (95% CI, 10.0 to 12.1) in the NALIRIFOX arm and 9.2 months (95% CI, 8.3 to 10.6) in the Gem+NabP arm (hazard ratio [HR] = 0.84 [95% CI, 0.71 to 0.99]; P = 0.040).

Median PFS was 7.4 months (95% CI, 6.0 to 7.7) in the NALIRIFOX arm and 5.6 months (95% CI, 5.3 to 5.8) in the Gem+NabP arm (HR = 0.70 [95% CI: 0.59, 0.85]; P = 0.0001). Additionally, ORR was 41.8% (95% CI, 36.8 to 46.9) in the NALIRIFOX arm and 36.2% (95% CI, 31.4 to 41.2) for the Gem+NabP group.

The FDA-recommended dosage for irinotecan liposome is 50 mg/m2 administered by intravenous infusion over 90 minutes every 2 weeks. Irinotecan liposome should be administered before oxaliplatin, fluorouracil, and leucovorin.

The most common adverse reactions in the NALIRIFOX arm were diarrhea, fatigue, nausea, vomiting, decreased appetite, abdominal pain, mucosal inflammation, constipation, and decreased weight. The most common laboratory abnormalities were decreased neutrophils, potassium, lymphocyte, and hemoglobin.

 

Reference:
FDA approves irinotecan liposome for first-line treatment of metastatic pancreatic adenocarcinoma. News release. US Food and Drug Administration; February 13, 2024. Accessed February 14, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-irinotecan-liposome-first-line-treatment-metastatic-pancreatic-adenocarcinoma.