Liposomal irinotecan (nal-IRI; Onivyde®; also known as pegylated liposomal irinotecan) has been developed with the aim of maximising anti-tumour efficacy while minimising drug-related toxicities compared with the conventional (non-liposomal) formulation of this topoisomerase 1 inhibitor. In combination with 5-fluorouracil and leucovorin (5-FU/LV), nal-IRI is the first agent to be specifically approved for use in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) who have progressed following gemcitabine-based therapy. In the pivotal, phase III NAPOLI-1 trial, intravenous administration of nal-IRI + 5-FU/LV to gemcitabine-pretreated patients with mPDAC (as a second-line treatment in approximately two-thirds of cases) was associated with a significant ≈ 2-month median overall survival advantage compared with 5-FU/LV alone. Moreover, adding nal-IRI to 5-FU/LV extended survival with a manageable safety profile and without adversely affecting health-related quality of life, thereby producing significant and clinically meaningful gains in quality-adjusted survival relative to 5-FU/LV alone. Complementing the observed efficacy and safety of nal-IRI in NAPOLI-1 are an increasing number of real-world studies, which provide evidence of the effectiveness of this combination therapy in the treatment of mPDAC that has progressed following gemcitabine-based therapy in contemporary clinical practice in Europe, the USA and East Asia. Thus, nal-IRI, in combination with 5-FU/LV, is the first regimen specifically approved for use as a second- or subsequent-line therapy in gemcitabine-pretreated patients with mPDAC and, as such, represents a valuable treatment option in this setting.
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During the peer review process, the manufacturer of liposomal irinotecan was also offered an opportunity to review this article. Changes resulting from comments received were made on the basis of scientific and editorial merit.
The preparation of this review was not supported by any external funding
Conflict of interest
James Frampton is a salaried employee of Adis International Ltd/Springer Nature, is responsible for the article content and declares no relevant conflicts of interest.
Enhanced material for this Adis Drug Evaluation can be found at https://doi.org/10.6084/m9.figshare.12270707.
The manuscript was reviewed by:D. Grapsa, National and Kapodistrian University of Athens, Athens, Greece; M. Harris, Department of Medical Oncology, Monash Health, Melbourne, Victoria, Australia; T. Macarulla, Gastrointestinal and Endocrine Tumor Unit, Vall d'Hebron University Hospital and Vall d'Hebron Institute of Oncology, Barcelona, Spain.
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Frampton, J.E. Liposomal Irinotecan: A Review in Metastatic Pancreatic Adenocarcinoma. Drugs 80, 1007–1018 (2020). https://doi.org/10.1007/s40265-020-01336-6