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Improved Overall Survival With Addition of Nanoliposomal Irinotecan to Fluorouracil/Leucovorin in Metastatic Pancreatic Cancer

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Key Points

  • The addition of nanoliposomal irinotecan to fluorouracil and leucovorin significantly improved overall survival in patients with metastatic pancreatic ductal cancer who had received gemcitabine-based therapy.
  • Toxicity was increased with the nanoparticle irinotecan combination regimen.

In the phase III NAPOLI-1 trial reported in The Lancet, Wang-Gillam et al found that the addition of nanoliposomal irinotecan (Onivyde) to fluorouracil (5-FU) and folinic acid (leucovorin) resulted in improved overall survival in patients with metastatic pancreatic ductal cancer who had received gemcitabine-based therapy. The trial results supported the recent approval of nanoliposomal irinotecan in combination with 5-FU/leucovorin in this setting.

Study Details

In this open-label trial, 417 patients from 76 sites in 14 countries were randomly assigned between January 2012 and September 2013 to receive nanoliposomal irinotecan alone at 120 mg/m² every 3 weeks (equivalent to 100 mg/m² of irinotecan base; n = 151), 5-FU/leucovorin (n = 149) or nanoliposomal irinotecan at 80 mg/m² (equivalent to 70 mg/m² of irinotecan base) plus 5-FU/leucovorin every 2 weeks (n = 117); the latter arm was added to the randomization scheme after protocol amendment.

Overall, 12% of patients received gemcitabine-based therapy in the adjuvant, neoadjuvant, or locally advanced setting but had not received previous treatment for metastatic disease, 56% had received one previous line of metastatic treatment, and 32% had received at least two lines of metastatic treatment.

Overall Survival

Efficacy comparisons for the nanoliposomal irinotecan plus 5-FU/leucovorin vs 5-FU/leucovorin group included only the 119 patients in the latter enrolled after the protocol amendment adding the irinotecan combination group. Median overall survival was 6.1 months (95% confidence interval [CI] = 4.8–8.9 months) in the nanoliposomal irinotecan combination group vs 4.2 months (95% CI = 3.3–5.3 months) in the 119 5-FU/leucovorin recipients (hazard ratio [HR] = 0.67, P = .012). Benefit was generally consistent across patient subgroups. Median overall survival was 4.9 months (95% CI = 4.2–5.6 months) in the nanoliposomal irinotecan monotherapy group vs 4.2 months (95% CI = 3.6–4.9 months) in the entire 5-FU/leucovorin group (HR = 0.99, P = .94).

Median progression-free survival was 3.1 months in the nanoliposomal irinotecan combination group vs 1.5 months in the 5-FU/leucovorin group (HR = 0.56, P = .0001) and 2.7 months in the nanoliposomal irinotecan monotherapy group vs 1.6 months in the 5-FU/leucovorin group (HR = 0.81, P = .1). Postprogression treatment was given to 31% of the nanoliposomal irinotecan plus 5-FU/leucovorin group to 38% of the comparator 5-FU/leucovorin group, with types of treatment being generally similar between the two groups.

Adverse Events

The most common grade 3 or 4 adverse events in the nanoliposomal irinotecan plus 5-FU/leucovorin group were neutropenia (27% vs 1% in the 5-FU/leucovorin group), fatigue (14% vs 4%), diarrhea (13% vs 4%), and vomiting (11% vs 3%). Serious adverse events occurred in 48% vs 45% of patients. Adverse events led to dose reduction in 33% vs 4% and to discontinuation in 11% vs 7%.

The investigators concluded: “Nanoliposomal irinotecan in combination with fluorouracil and folinic acid extends survival with a manageable safety profile in patients with metastatic pancreatic ductal adenocarcinoma who previously received gemcitabine-based therapy. This agent represents a new treatment option for this population.”

The study was funded by Merrimack Pharmaceuticals.

Li-Tzong Chen, MD, of the National Health Research Institutes, Taiwan, is the corresponding author of The Lancet article.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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