Treatment Effect and Safety of Nanoliposomal Irinotecan with Fluorouracil and Folinic Acid after Gemcitabine-Based Therapy in Patients with Advanced Pancreatic Cancer: A Multicenter, Prospective Observational Study

Abstract

Although the combination of nanoliposomal irinotecan plus fluorouracil/folinic acid (nal-IRI/FF) exhibited survival benefits in gemcitabine-refractory patients with advanced pancreatic cancer (APC) in the phase III NAPOLI-1 trial, there is limited data on the efficacy and safety of this regimen in real-world settings in Japan. This multicenter, prospective observational study enrolled patients with APC who received nal-IRI/FF after a gemcitabine-based regimen from July 2020 to June 2021. We collected and analyzed clinical data and conducted survival and multivariate analyses. Thirty-one (78%) of the 40 patients had metastases. Nal-IRI/FF was the second-line therapy in 36 patients (90%). The median duration was 3.2 months. The disease control rate was 57%. The median progression-free survival and overall survival (OS) were 4.5 months (95% confidence interval [CI]: 2.8−5.5) and 7.4 months (95% CI: 5.1−10.6), respectively. Common ≥grade 3 toxicities included neutropenia (28%) and fatigue (23%). Fatigue led to treatment discontinuation in 6 out of 10 patients. Multivariate analysis showed that a neutrophil-to-lymphocyte ratio > 4 was a significant risk factor for a short OS (hazard ratio (HR) = 3.08, 95% CI: 1.21−7.85, p = 0.02). In conclusion, nal-IRI/FF is an appropriate treatment option for APC following gemcitabine-containing regimens.

Keywords: advanced pancreatic cancer; nanoliposomal irinotecan; second-line therapy.

Figure 1

Kaplan–Meier survival analyses. (a) Progression-free survival (PFS) of all patients. (b) Overall survival (OS) of all patients; CI, confidence interval, and p-value were calculated using the log-rank test.

Figure 2

Kaplan–Meier survival analyses. (a) Overall survival (OS) with the best response = progressive disease (PD) versus stable disease (SD) or partial response (PR). (b) OS with treatment discontinuation versus without discontinuation. (c) OS with performance status (PS) = 0 versus PS = 1, 2. (d) OS with neutrophil-lymphocyte ratio (NLR) > 4 versus NLR ≤ 4. mOS, median overall survival; HR, hazard ratio. p-value was calculated using the log-rank test.