Liposomal Irinotecan: A Review as First-Line Therapy in Metastatic Pancreatic Adenocarcinoma
Michael B. Brown, Hannah A. Blair
Abstract
Liposomal irinotecan (Onivyde®), also known as liposomal pegylated irinotecan, has been developed with the intent of maximising anti-tumour efficacy and minimising drug-related toxicities compared with conventional formulations of this topoisomerase 1 inhibitor. In combination with fluorouracil, leucovorin and oxaliplatin (NALIRIFOX), liposomal irinotecan is approved in the USA and the EU for first-line therapy of eligible patients with metastatic pancreatic adenocarcinoma. In a phase III clinical trial, NALIRIFOX significantly improved overall survival (OS) and progression free survival (PFS) compared with gemcitabine plus nanoparticle albumin bound paclitaxel (nab-paclitaxel) as first-line treatment of patients with metastatic pancreatic ductal adenocarcinoma (mPDAC). The safety profile of NALIRIFOX was generally manageable, with diarrhoea, hypokalaemia and neutropenia being the most common grade ≥ 3 treatment-emergent adverse events. Although further analyses will help position the liposomal irinotecan-containing regimen NALIRIFOX in first-line treatment of metastatic pancreatic adenocarcinoma, current evidence indicates that it is a useful addition to treatment options in this patient population. Pancreatic adenocarcinoma is an invasive tumour arising from the pancreas. Generally, pancreatic adenocarcinoma is diagnosed in later stages having spread to distant sites (advanced/metastatic disease). Liposomal irinotecan (Onivyde®), also known as liposomal pegylated irinotecan, is a liposomal formulation of the topoisomerase 1 inhibitor irinotecan. Encapsulation in liposomes aims to improve the activity and tolerability of irinotecan by protecting the drug in circulation and improving delivery to tumours. When given to adults with metastatic pancreatic ductal adenocarcinoma (mPDAC) in a clinical trial, a combination of liposomal irinotecan, fluorouracil, leucovorin and oxaliplatin (NALIRIFOX) improved survival outcomes compared with the established first-line treatment combination of gemcitabine plus nanoparticle bound albumin paclitaxel (nab-paclitaxel) and had a generally manageable safety profile. Although further analyses will help position the liposomal irinotecan-containing regimen NALIRIFOX in first-line treatment of metastatic pancreatic adenocarcinoma, current evidence indicates that is a useful addition to treatment options in this patient population.