Nanoliposomal irinotecan with fluorouracil and folinic acid, FOLFIRINOX, and S-1 as second-line treatment for unresectable pancreatic cancer after gemcitabine plus nab-paclitaxel: a pooled analysis of two retrospective studies in Japan
Authors: Shibuki Taro , Otsuka Taiga , Shimokawa Mototsugu , Nakazawa Junichi , Arima Shiho , Fukahori Masaru , Miwa Keisuke , Okabe Yoshinobu , Koga Futa , Ueda Yujiro , Kubotsu Yoshihito , Makiyama Akitaka , Shimokawa Hozumi , Takeshita Shigeyuki , Nishikawa Kazuo , Komori Azusa , Otsu Satoshi , Hosokawa Ayumu , Tatsunori Sakai , Oda Hisanobu , Kawahira Machiko , Arita Shuji , Honda Takuya , Taguchi Hiroki , Tsuneyoshi Kengo , Kawaguchi Yasunori , Fujita Toshihiro , Sakae Takahiro , Nio Kenta , Ide Yasushi , Ureshino Norio , Shirakawa Tsuyoshi , Mizuta Toshihiko , Mitsugi Kenji 
Published: July 2023

Abstract
Background:
Few standard second-line treatment options have been established yet for the treatment of patients with unresectable pancreatic cancer refractory to first-line gemcitabine plus nab–paclitaxel (GnP) therapy. The aim of this study was to compare the outcomes of treatment with nanoliposomal irinotecan + 5-fluorouracil/folinic acid (Nal-IRI + 5-FU/LV), S-1, and FOLFIRINOX as second-line regimens in unresectable pancreatic cancer patients previously treated with first-line GnP therapy.
Methods:
This was a pooled analysis of two multicenter retrospective studies; the NAPOLEON-1 study, in which unresectable pancreatic cancer patients who had received FOLFIRINOX or GnP as first-line treatment were enrolled, and the NAPOLEON-1 study (retrospective part), in which unresectable pancreatic cancer patients who had received Nal-IRI + 5-FU/LV as second-line treatment were enrolled. The treatment efficacies of the second-line regimens were evaluated by determination of the overall survival (OS) and progression-free survival (PFS) of the patients.
Results:
Data of a total of 318 patients who had received Nal-IRI + 5-FU/LV (n = 102), S-1 (n = 57), or FOLFIRINOX (n = 14) as second-line treatment were included in this analysis. The median OS in the Nal-IRI + 5-FU/LV group was 9.08 months, while it was significantly worse, at 4.90 months (P = 0.002), in the S-1 group. The median OS in the FOLFIRINOX group was 4.77 months (P = 0.484), and the difference between FOLFIRINOX and Nal-IRI + 5-FU/LV was not statistically significant. Subgroup analyses revealed that in most subgroups, the median OS was better in the patients treated with Nal-IRI + 5-FU/LV than in those treated with S-1. However, a statistical interaction was observed between the treatment regimen and serum Alb < 3.5 g/dL (P = 0.042) and serum CRP ≥ 0.3 mg/dL (P = 0.006). In terms of the PFS, the median PFS was 2.93 months in the Nal-IRI + 5-FU/LV group and significantly worse, at 2.53 months (P = 0.024), in the S-1 group; the FOLFIRINOX group showed a comparable median PFS of 3.04 months (P = 0.948) to that in the Nal-IRI + 5-FU/LV group. Multivariate analysis identified the serum CRP, serum CA19-9, duration of first-line GnP therapy, and use (yes/no) of S-1 for second-line treatment as independent predictors of the OS.
Conclusions:
Second-line Nal-IRI + 5-FU/LV therapy yielded a more favorable OS than second-line S-1 therapy, however, it is still important to consider the patient background characteristics while selecting the most appropriate treatment.