Irinotecan Liposome Approved for First-Line Metastatic Pancreatic Adenocarcinoma Treatment

Joseph Kalis, PharmD, BCOP.

The FDA has approved irinotecan liposome (Onivyde®, Ipsen Biopharmaceuticals, Inc.) with oxaliplatin, fluorouracil, and leucovorin, for the first-line treatment of metastatic pancreatic adenocarcinoma.  

Why it matters: “The approval of liposomal irinotecan in combination with standard-of-care agents provides clinicians and patients with another option for first-line treatment of metastatic pancreatic cancer,” wrote Joseph Kalis, PharmD, BCOP, an Ambulatory Oncology Pharmacy Specialist at the University of Colorado Health. “This malignancy can be difficult to treat, so it’s very important to have proven therapies that can be tailored to each patient.”

What they studied: Efficacy was evaluated in the multicenter, open-label, active-controlled NAPOLI-3 trial (NCT04083235), in which 770 patients with metastatic pancreatic adenocarcinoma who had not previously received chemotherapy in the metastatic setting were enrolled. Patients were randomized 1:1—stratified by region, liver metastases, and Eastern Cooperative Oncology Group (ECOG) performance status—to receive either:

  • An intravenous infusion of irinotecan liposome 50 mg/m2 over 90 minutes, followed by oxaliplatin 60 mg/m2 over 120 minutes, followed by leucovorin 400 mg/m2 over 30 minutes, followed by fluorouracil 2,400 mg/m2 over 46 hours, every two weeks. This was known as the NALIRIFOX arm
  • An intravenous infusion of nab-paclitaxel (NabP) 125 mg/m2 over 35 minutes, followed by gemcitabine (Gem) 1,000 mg/m2 over 30 minutes on Days 1, 8, and 15 of each 28-day cycle. This was known as the Gem plus NabP arm

The primary end point studied was overall survival, in addition to the secondary end points of progression-free survival and objective response rate.

What they found: Statistically significant improvements of overall survival and progression-free survival were seen in the NALIRIFOX arm compared to the Gem plus NabP arm.

  • The median overall survival in the NALIRIFOX arm was 11.1 months compared with 9.2 months in the Gem plus NabP arm
  • The median progression-free survival in the NALIRIFOX arm was 7.4 months compared with 5.6 months in the Gem plus NabP arm

Additionally, the objective response rate was seen at 41.8% in the NALIRIFOX arm compared with 36.2% in the Gem plus NabP arm.

Adverse events: The most common adverse reactions experienced in ≥20% of those receiving NARLIRIFOX—with a difference between arms of ≥5% for all grades or ≥2% for grades 3 or 4 compared to those receiving Gem plus NabP—were diarrhea, fatigue, nausea, vomiting, decreased appetite, abdominal pain, mucosal inflammation, constipation, and decreased weight. The most common laboratory abnormalities, with ≥10% being grade 3 or 4, were decreased neutrophils, decreased potassium, decreased lymphocytes, and decreased hemoglobin.

Conclusion: “I would be curious to see if future data allows us to compare NALIRIFOX to standard-of-care FOLFIRINOX (leucovorin/fluorouracil/irinotecan/oxaliplatin)—with standard irinotecan—as it remains to be seen what payor coverages will be for NALIRIFOX,” concluded Dr. Kalis.

Instructions: The recommended dosage of irinotecan liposome is 50 mg/m2 via intravenous infusion over 90 minutes every two weeks. Additionally, irinotecan liposome should be administered before oxaliplatin, fluorouracil, and leucovorin. As well, it is noted that there is no recommended dosage of irinotecan liposome for patients with serum bilirubin above the upper limit of normal.

For More Information

Wainberg ZA, Melisi D, Macarulla T, et al (2023). NALIRIFOX versus nab-paclitaxel and gemcitabine in treatment-naive patients with metastatic pancreatic ductal adenocarcinoma (NAPOLI 3): a randomised, open-label, phase 3 trial. Lancet, 402(10409):1272-1281. DOI:10.1016/S0140-6736(23)01366-1 (2024). A study to assess the effectiveness and safety of irinotecan liposome injection, 5-fluorouracil/leucovorin plus oxaliplatin in patients not previously treated for metastatic pancreatic cancer, compared to nab-paclitaxel+gemcitabine treatment (NAPOLI 3). NLM identifier: NCT04083235.

Onivyde® (irinotecan liposome) prescribing information (2024). Ipsen Biopharmaceuticals, Inc. Available at:

US Food and Drug Administration (2024). FDA approves irinotecan liposome for first-line treatment of metastatic pancreatic adenocarcinoma. Available at: 

Image credit: Ed Uthman. Licensed under CC BY 2.0

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