Second-line and third-line therapy with nanoliposomal irinotecan (nal-IRI) in pancreatic cancer: a single-center experience and review of literature

Abstract

Background: Prognosis of patients with pancreatic cancer is still extremely poor. First-line palliative therapies with FOLFIRINOX or gemcitabine/nab-paclitaxel have been established in the last decade. In the second-line, 5-FU/LV in combination with nanoliposomal irinotecan (nal-IRI) after gemcitabine has been shown to be effective. However, the use of nal-IRI as third-line therapy after FOLFIRINOX and gemcitabine-based chemotherapies is still controversial. In this study, we report about the use of 5-FU/LV + nal-IRI in a daily practice and analyze whether nal-IRI is an option as third-line therapy after FOLFIRINOX and gemcitabine/nab-paclitaxel.Methods: This is a single center retrospective analysis of patients with irresectable pancreatic cancer who were treated with 5-FU/LV and nal-IRI from 2017 to 2021 as second-or third-line palliative treatment.Overall survival (OS), progression-free survival (PFS) and toxicity were analyzed, and multivariate analysis was used to identify independent prognostic factors.Results: Twenty-nine patients receiving 5-FU/LV and nal-IRI were included in the analysis. The majority of patients (n=19) received 5-FU/nal-IRI as third-line therapy after pre-exposition to FOLFIRINOX and gemcitabine/nab-paclitaxel. Median OS and PFS were 9.33 months (95% CI: 3.37, 15.30) and 2.90 months (95% CI: 1.64, 4.16), respectively. Furthermore, patients receiving nal-IRI + 5-FU/LV as thirdline treatment also showed some benefits, with no OS difference compared to second-line patients (9.33 vs. 10.27 months; HR: 1.85; 95% CI: 0.64, 5.41; P=0.253). Adverse effects were similar to reported trials.Conclusions: In our study, the use of 5-FU/nal-IRI in unselected patients with advanced pancreatic cancer showed similar OS, PFS and tolerance as randomized prospective phase II/III trials. Interestingly, the use of 5-FU/nal-IRI seemed to be beneficial in third-line therapy, despite a pre-exposure to non-liposomal irinotecan.

Use of Paclitaxel Associated to Lipid Core Nanoparticles (LDE) in the Second or Third Line Treatment of Advanced Pancreatic Adenocarcinoma

“…Although it was not feasible to objectively evaluate in our patients the treatment responses by imaging exams, the data on the overall survival after the beginning of LDE-paclitaxel therapy suggest that this treatment is not inferior to other chemotherapeutic approaches to the disease. In this respect, in treatments of patients with PAC, Wu (2015) tested Neratinib plus Lapatinib and capecitabine and reported median overall survival 5.2 months [23]; Cardin (2018), 4.57 months with ganetespib [24]; Mie (2021), 4.6 months with erlotinib plus gemcitabine [19]; Mohring (2023) with liposomal irinotecan plus 5-fluorouracil, 9.33 months [25]. Relative to commercial formulations of paclitaxel, in second or third line treatments of PAC, Tajima (2018) reported 0.77 months with lowdose paclitaxel [20] and Hosein (2013) reported 7.3-month overall survival with nab-paclitaxel [22].…”