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Background and objective: Chemotherapy with 5-fluoruracil (5-FU)/folinic acid (FA), irinotecan (IRI) and oxaliplatin (OX) (FOLFIRINOX) is a standard first line treatment in advanced pancreatic cancer. Recently, an alternative regimen with nanoliposomal irinotecan (nal-IRI) (NALIRIFOX) has shown benefit over gemcitabine and nab-paclitaxel (GN) in treatment-naïve metastatic patients (pts). Accordingly, clinical practice guidelines have incorporated both, FOLFIRINOX and NALIRIFOX, as possible first line therapeutic options. In clinical practice, it is difficult to choose one regimen over the other, as there is neither a direct comparison nor any data analyzing the sequential use of NALIRIFOX and FOLFIRINOX.

Method: In this retrospective study, pancreatic cancer pts who were recommended a nal-IRI containing therapy by a multidisciplinary tumor board of a tertiary care center in Germany were screened between 01/2023 and 06/2025. Cases were included if they had a history of FOLFIRINOX treatment and at least one cycle of a nal-IRI based chemotherapy regimen. Stagings were performed after 1-4 months. The primary outcomes of interest were progression free survival (PFS) and overall survival (OS). Exploratory outcomes included disease control and secondary resectability rate.

Result: A total of 21 pts with histologically proven pancreatic cancer were included in the study. Prior to nal-IRI, pts received a median of 7 cycles of FOLFIRINOX. Other frequent therapies that were applied before or after FOLFIRINOX were GN (n=10) and surgery (n=9). Following the multidisciplinary tumor board recommendation, 12 pts received NALIRIFOX and 9 patients received other nal-IRI based regimen (nal-IRI with 5-FU/FA (n=7) or capecitabine (n=2)) with a median of 6 cycles and a median follow-up time of 14.5 months at the time of analysis.Median PFS was 10.8 months, median OS was 14.2 months. The disease control rate was 80.95%.7 patients were locally advanced and received nal-IRI with neoadjuvant intention after FOLFIRINOX failed to achieve resectability. Of those, 3 patients achieved resectability with nal-IRI, the remaining 4 patients changed regimen before progression.

Summary: NALIRIFOX and nal-IRI based regimen as sequential therapy after FOLFIRINOX show promising PFS and OS and may therefore be a therapeutic option option in metastasized or neoadjuvant settings. Despite the similarity of the regimen, sequential therapy achieved disease control in the majority and secondary resectability in some of the patients.