Efficacy and safety of nanoliposomal irinotecan plus fluorouracil and folinic acid after irinotecan-based chemotherapy in patients with advanced pancreatic cancer: Results of the retrospective part of the NAPOLEON-2 study.
Authors: Kawaguchi Yasunori , Aikawa Tomomi , Shimokawa Mototsugu , Otsuka Taiga , Shibuki Taro , Nakazawa Junichi , Arima Shiho , Miwa Keisuke , Koga Futa , Ueda Yujiro , Kubotsu Yoshihito , Shimokawa Hozumi , Takeshita Shigeyuki , Nishikawa Kazuo , Hosokawa Ayumu , Oda Hisanobu , Sakai Tatsunori , Shirakawa Tsuyoshi , Mizuta Toshihiko , Mitsugi Kenji 
Published: January 2023

705 Background: Nanoliposomal irinotecan plus fluorouracil and folinic acid (nal-IRI/FU/LV; NFF) is the standard regimen after gemcitabine-based therapy for unresectable or recurrent pancreatic cancer (urPC). However, the efficacy and safety of NFF in patients who previously received irinotecan-based chemotherapy remain unclear. Methods: This retrospective study collected data from patients with urPC who received at least one previous chemotherapy before receiving NFF therapy at 21 hospitals in Japan between June 2020 and May 2021 (NAPOLEON-2 study). We analyzed antitumor efficacy, progression-free survival (PFS), and overall survival (OS) after the initiation of NFF and compared adverse events (AEs) between previous irinotecan users and non-users. Results: NFF was administered to 161 patients. The median follow-up period was 7.3 months (95% confidence interval [CI] = 5.6–8.9). All patients received prior gemcitabine-based therapy, and NFF was administered as the second-, third-, and fourth-or-later-line chemotherapy in 104, 41, and 16 patients, respectively. Eighteen patients (11%) previously received irinotecan. Patients’ characteristics did not significantly differ between irinotecan users (n = 18) and non-users (n = 143), excluding age (mean [range], 64 [38–78] vs. 68 [47–85] years; p = 0.01), the lung metastasis rate (44% vs. 14%; p < 0.01), the treatment line (2nd/3rd/4th-or-later, 0%/56%/44% vs. 73%/22%/6%; p < 0.01), and the pretreatment period (15.3 [6.8–45.0] vs. 9.1 [1.4–36.2] months; p < 0.01). The median relative dose intensities of nal-IRI were 87.1% and 81.1% in irinotecan users and non-users, respectively (p = 0.28), and those of FU were 93.5% and 89.2%, respectively (p = 0.54). The objective response rate (6% vs. 5%; p = 0.90), disease control rate (44% vs. 53%; p = 0.49), PFS (2.8 months vs. 3.6 months; hazard ratio [HR] = 1.23; 95% CI = 0.74–2.05; p = 0.42), and OS (9.2 months vs. 8.0 months; HR = 0.88; 95% CI = 0.49–1.57; p = 0.66) did not differ between irinotecan users and non-users, nor did the rates of Grade 3/4 hematological (p = 0.68) and non-hematological (p = 0.13) AEs. Among irinotecan users, the duration of irinotecan-based therapy and the irinotecan-free interval before NFF did not affect the efficacy of NFF. Conclusions: NFF might be effective and safe even in patients with urPC who received irinotecan-based chemotherapy irrespective of its duration or the interval to NFF. Therefore, NFF is a possible treatment option after irinotecan-based chemotherapy. Further studies with a sufficient number of patients and a prospective design are warranted to examine the efficacy of NFF after irinotecan-based chemotherapy.