Liposomal Irinotecan Receives FDA Approval for First-Line Treatment of Stage 4 Pancreatic Cancer

On 13 February 2024, the United States Food and Drug Administration (FDA) approved first-line treatment of metastatic pancreatic adenocarcinoma with liposomal irinotecan (Onivyde) combined with oxaliplatin, fluorouracil, and leucovorin.

On 22 October 2015, the FDA had previously approved Onivyde with 5FU and leucovorin for patients with advanced pancreatic cancer previously treated with gemcitabine-based chemotherapy.

Nanotechnology has been used to manufacture drugs in our clinical practice for around 20 years. Onivyde is the third FDA-approved chemotherapy drug produced using nanotechnology; Abraxane and Doxil are also produced using this technology.

This new form was created by coating conventional irinotecan chemotherapy with liposomal micelles using nanotechnological methods.

FDA Approval Based on NAPOLI 3

Efficacy was evaluated in NAPOLI 3, a randomized, multicenter, open-label, active-controlled study of 770 patients with metastatic pancreatic adenocarcinoma who had not previously received chemotherapy in the metastatic setting.

Randomization was based on region, liver metastases, and ECOG performance status. Patients were assigned to one of the following treatments:

• NALIRIFOX (known in Turkey as FOLFIRINOX ): irinotecan liposome 50 mg/m2 by intravenous infusion over 90 minutes, followed by oxaliplatin 60 mg/m2 by intravenous infusion over 120 minutes, leucovorin 400 mg/m2 intravenously over 30 minutes, and fluorouracil 2400 mg/m2 intravenously over 46 hours, every 2 weeks.
• Gem+NabP: nab-paclitaxel 125 mg/m2 by 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.

Results

The primary efficacy outcome was overall survival (OS). Additional measures were investigator-assessed progression-free survival (PFS) and objective response rate.

NAPOLI 3 demonstrated statistically significant improvements in overall survival and PFS with NALIRIFOX compared with Gem+NabP.

• Median OS was 11.1 months with NALIRIFOX (95% CI: 10.0, 12.1) versus 9.2 months with Gem+NabP (95% CI: 8.3, 10.6) (hazard ratio [HR] 0.84 [95% CI: 0.71, 0.99]; p-value 0.0403).
• Median PFS was 7.4 months with NALIRIFOX (95% CI: 6.0, 7.7) versus 5.6 months with Gem+NabP (95% CI: 5.3, 5.8) (HR 0.70 [95% CI: 0.59, 0.85]; p-value 0.0001).
• Objective response rates were 41.8% with NALIRIFOX (95% CI: 36.8, 46.9) and 36.2% with Gem+NabP (95% CI: 31.4, 41.2).

The most common NALIRIFOX side effects (occurring in more than 20% at any grade, with an any-grade difference of at least 5% or a grade 3 or 4 difference of at least 2% compared with Gem+NabP) were diarrhea, fatigue, nausea, vomiting, decreased appetite, abdominal pain, mucosal inflammation, constipation, and weight loss. The most common laboratory abnormalities (10% grade 3 or 4) were decreased neutrophils, potassium, lymphocytes, and hemoglobin.

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