Second-Line Nanoliposomal Irinotecan Combination Promising In Metastatic Pancreatic Cancer

Metastatic pancreatic cancer patients who have progressed on gemcitabine-based regimens could benefit from a combination of nanoliposomal irinotecan, fluorouracil and folinic acid

medwireNews: Addition of nanoliposomal irinotecan to fluorouracil and folinic acid improves survival outcomes in patients with metastatic gemcitabine-resistant pancreatic ductal adenocarcinoma, suggest phase III trial results.

Researcher Li-Tzong Chen, from the National Institute of Cancer Research in Tainan, Taiwan, and fellow investigators explain that “[n]anoliposomal irinotecan comprises irinotecan free base encapsulated in liposome nanoparticles”, which keeps the drug in circulation for longer than unencapsulated irinotecan and results in increased intratumoural levels of both irinotecan and its active metabolite SN-38.

The phase III NAPOLI-1 trial included 417 patients with metastatic pancreatic ductal adenocarcinoma who had previously received gemcitabine-based therapy in the neoadjuvant, adjuvant, locally advanced or metastatic setting. Study participants were randomly assigned to receive either open-label nanoliposomal irinotecan 80 mg/m2 followed by fluorouracil and folinic acid every 2 weeks, nanoliposomal irinotecan 120 mg/m2 alone once every 3 weeks, or fluorouracil and folinic acid (control).

Overall survival (OS) and progression-free survival (PFS) were significantly longer for the 117 patients given the triple regimen than for the 149 treated with fluorouracil plus folinic acid, at a median of 6.1 versus 4.2 months and 3.1 versus 1.5 months, respectively.

The addition of nanoliposomal irinotecan also significantly improved time to treatment failure (2.3 vs 1.4 months) and the objective response rate (16 vs 1%).

The 151 study participants treated with nanoliposomal irinotecan monotherapy had OS, PFS and time to treatment failure times that were similar to the control group, but the objective response rate (6%) was significantly higher. This, says the team, suggests that “nanoliposomal irinotecan alone has some activity against pancreatic cancer”.

Among patients who received nanoliposomal irinotecan plus fluorouracil and folinic acid, the most frequent grade 3 or 4 toxicities were neutropenia (27%), fatigue (14%), diarrhoea (13%) and vomiting (11%).

Treatment-related serious adverse events occurred in 48% of patients in the triple therapy group compared with a rate of 45% in the fluorouracil plus folinic acid group, while the corresponding rates for discontinuation owing to toxicity were 11% and 7%.

But despite the additional toxicity, the researchers note that “the quality of life of patients assigned nanoliposomal irinotecan plus fluorouracil and folinic acid was not appreciably different from those allocated the fluorouracil and folinic acid control”, an important consideration in this patient population.

They conclude in The Lancet that this triple regimen represents a potential second-line treatment option for patients with metastatic pancreatic cancer.

The authors of an accompanying comment note that the combination of nanoliposomal irinotecan, fluorouracil and folinic acid caused “little neurotoxicity”, making this trio a suitable option after first-line albumin-bound paclitaxel plus gemcitabine, which can result in substantial neurotoxicity.

“This schedule would give the patient a break from this debilitating and cumulative adverse event, and pave the way for possible third-line administration of oxaliplatin plus fluorouracil and folinic acid”, write Helmut Oettle, from Zentrum für Tumormedizin in Friedrichshafen, Germany, and Thorsten Lehmann, from Klinikum Friedrichshafen in Germany.

The commentators conclude that this sequence “could also represent an overall therapeutic strategy, thereby providing patients with ongoing effective options.”


Wang-Gillam A, Li C-P, Bodoky G, et al. Nanoliposomal irinotecan with fluorouracil and folinic acid in metastatic pancreatic cancer after previous gemcitabine-based therapy (NAPOLI-1): a global, randomised, open-label, phase 3 trial.Lancet 2015; Advance online publication 22 November. doi:

Oettle H, Lehmann T. Gemcitabine-resistant pancreatic cancer: a second-line option. Lancet 2015; Advance online publication 22 November. doi:

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