Changing treatment outcomes in metastatic and recurrent pancreatic cancer: a real-world comparison before and after the availability of nanoliposomal irinotecan

Abstract Background While nanoliposomal irinotecan (nal-IRI) plus 5-fluorouracil and leucovorin (5-FU/LV) showed higher efficacy than 5-FU/LV in controlled settings, whether the availability of this regimen has truly improved real-world survival outcomes in unresectable pancreatic cancer remains unclear. Methods We retrospectively analyzed consecutive patients with metastatic or recurrent pancreatic cancer, who received second-line chemotherapy after gemcitabine with nab-paclitaxel (GnP) between April 2015 and September 2024 at our hospital. The patients were divided into two cohorts: patients treated before (Group A) and after (Group B) the availability of nal-IRI plus 5-FU/LV in Japan. Time to treatment failure (TTF) of first-line GnP, overall survival (OS), and progression-free survival (PFS) were compared between groups. OS from the beginning of first-line treatment (OS-1) and from the beginning of second-line treatment (OS-2) were evaluated. Results A total of 426 patients (Group A/B: 230/196) were included. Median TTF were comparable (6.4/6.6 months, P = .75). However, median second-line PFS and OS-2 were significantly longer in Group B (PFS: 3.0/4.8 months, P = .03; OS-2: 6.3/8.2 months, P = .047). Median OS-1 tended to be longer in Group B (13.9/17.2 months, P = .07). Multivariate analysis revealed that treatment after the introduction of nal-IRI plus 5-FU/LV was an independent prognostic factor for OS-2 (hazard ratio, 0.75; P < .01). Conclusion The introduction of nal-IRI plus 5-FU/LV was associated with improved second-line treatment outcomes, providing a new combination regimen with acceptable toxicity in metastatic or recurrent pancreatic cancer.