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

Christian Möhring; Freddy José Frontado Graffe; Alexandra Bartels; Farsaneh Sadeghlar; Taotao Zhou; Robert Mahn; Milka Marinova; Georg Feldmann; Peter Brossart; Tim R Glowka; Jörg C Kalff; Christian P Strassburg; Maria A Gonzalez-Carmona

doi:10.21037/jgo-22-632

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

J Gastrointest Oncol. 2023 Feb 28;14(1):352-365. doi: 10.21037/jgo-22-632. Epub 2023 Feb 15.

Affiliations

¹ Department of Internal Medicine I, University Hospital Bonn, Bonn, Germany.
² Department of Nuclear Medicine, University Hospital Bonn, Bonn, Germany.
³ Department of Internal Medicine III, University Hospital Bonn, Bonn, Germany.
⁴ Department of Visceral Surgery, University Hospital Bonn, Bonn, Germany.

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 third-line 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.

Keywords: FOLFIRINOX; irinotecan resistance; nal-irinotecan; palliative chemotherapy; pancreatic cancer.