Irinotecan Liposome Approved by FDA for First-Line Treatment of Metastatic Pancreatic Adenocarcinoma

Irinotecan Liposome Approved by FDA for First-Line Treatment of Metastatic Pancreatic Adenocarcinoma

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

This approval was based on findings from NAPOLI 3 (NCT04083235), a randomized, multicenter, open-label, active-controlled trial that included 770 patients with metastatic pancreatic adenocarcinoma without prior treatment with chemotherapy in the metastatic setting, according to an alert from the FDA. Patients were randomized 1:1 to receive either NALIRIFOX or nab-paclitaxel plus gemcitabine.

The main efficacy outcome measure of the NAPOLI 3 trial was overall survival (OS). Other efficacy measures included objective response rate (ORR) and investigator-assessed progression-free survival (PFS).

Findings from the trial demonstrated that NALIRIFOX significantly improves ORR and PFS compared with nab-paclitaxel plus gemcitabine. The median OS for patients in the NALIRIFOX arm was 11.1 months (95% CI, 10.0-12.1) compared with 9.2 months (95% CI, 8.3-10.6) in the nab-paclitaxel plus gemcitabine arm (HR = 0.84; 95% CI, 0.71-0.99; P = .0403).

The median PFS was 7.4 months (95% CI, 6.0-7.7) in patients assigned NALIRIFOX vs 5.6 months (95% CI, 5.3-5.8) in those assigned nab-paclitaxel plus gemcitabine (HR = 0.70; 95% CI, 0.59-0.85; P = .0001). Patients in the NALIRIFOX group had an ORR of 41.8% (95% CI, 36.8%-46.9%) compared with 36.2% (95% CI, 31.4%-41.2%) in those in the nab-paclitaxel plus gemcitabine group.

In particular, NALIRIFOX consisted of irinotecan liposome 50 mg/m2 as an intravenous fusion delivered over a 90-minute period, followed by 60 mg/m2 of oxaliplatin intravenously for 120 minutes, followed by 400 mg/m2 leucovorin intravenously over 30 minutes, then 2400 mg/m2 of fluorouracil over 46 hours. This specific regimen was administered to patients every 2 weeks. For those in the other assignment group, patients were given 125 mg/m2 of nab-paclitaxel intravenously over 35 minutes followed by 1000 mg/m2 of gemcitabine intravenously over 30 minutes on days 1, 8, and 15 of each 28-day cycle, according to the alert.

The most common adverse reactions with NALIRIFOX, which occurred in at least 20% of patients in this trial, with a difference between arms of at least 5% for all grades or at least 2% for grades 3 and 4 compared with nab-paclitaxel plus gemcitabine, included fatigue, diarrhea, vomiting, nausea, abdominal pain, decreased appetite, constipation, mucosal inflammation, and decreased weight. The most common laboratory abnormalities, which were considered grades 3 or 4 in at least 10% of patients, included decreased potassium levels, decreased neutrophil levels, decreased hemoglobin levels, and decreased lymphocyte levels.

According to the FDA alert, the recommended dose of irinotecan liposome is 50 mg/m2 given via intravenous infusion over 90 minutes every 2 weeks. Of note, irinotecan liposome should be administered before fluorouracil, oxaliplatin, and leucovorin. A recommended dosage of irinotecan liposome has not been determined for patients with serum bilirubin above the upper limit of normal.

The FDA noted that this application was previously granted orphan drug designation.

Reference

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