Effect of biliary drainage and biliary tract infection in unresectable pancreatic cancer treated with nanoliposomal irinotecan with fluorouracil and folinic acid: a multicenter, prospective cohort study (NAPOLEON-2)

Background: The effectiveness and safety of nanoliposomal irinotecan with fluorouracil and folinic acid (NFF) in patients with unresectable or recurrent pancreatic cancer with or without prior biliary drainage (BD) or on-treatment biliary tract infection (BTI) in the real world are unclear. Therefore, we analyzed the clinical outcomes of this condition in a multicenter, prospective study (NAPOLEON-2). Methods: We evaluated 150 patients with unresectableor recurrent pancreatic cancer who received NFF as second- or later-line therapy. The patients were categorized into the pre-treatment BD group (37 patients) and the non-BD group (113 patients). The primary endpoint was overall survival (OS). Secondary endpoints were progression-free survival (PFS), the objective response rate (ORR), the disease control rate (DCR), relative dose intensity, and adverse events (AEs). BTI was estimated using landmark analysis at 2 and 3 months to reduce immortal bias. Results: There was no difference in OS between the two groups (hazard ratio, 1.25; 95% confidence interval, 0.83–1.89), and PFS was not different between the groups. Hematological AEs of grade ≥ 3 were observed in 34% of patients in the non-BD group and 38% in the BD group, while nonhematological AEs of grade ≥ 3 were observed in 40% and 68%, respectively. The BTI rate was higher in the BD group than in the non-BD group (30% vs 4%). On-treatment BTI showed no clinically meaningful difference in OS at the 2- and 3-month landmark analyses. Conclusions: BD has little effect on survival in patients treated with NFF. Physicians need to pay attention to BTI in NFF treatment.