Real-world evidence of nanoliposomal irinotecan and fluorouracil with folinic acid in patients with unresectable or recurrent pancreatic cancer: Final results of a multicenter observational study.
Authors: Yudai Shinohara, Tsuyoshi Shirakawa, Mototsugu Shimokawa, Taiga Otsuka, Hozumi Shimokawa, Junichi Nakazawa, Futa Koga, Hisanobu Oda, Shigeyuki Takeshita, Shiho Arima, Shuji Arita, Yasunori Kawaguchi, Kazuo Nishikawa, Hiroki Taguchi, Kenichi Jikuya, Tatsunori Sakai, Yujiro Ueda, Takahiro Sakae, Toshihiko Mizuta, Kenji Mitsugi
Journal: Journal of Clinical Oncology (2025)

721 Background: Nanoliposomal irinotecan (NAL-IRI) and fluorouracil with folinic acid (NFF) is the standard regimen after gemcitabine-based therapy for unresectable or recurrent pancreatic cancer (urPC). However, we have almost no prospective data on its efficacy and safety in the real-world, so we conducted this study to investigate them both retrospectively and prospectively (NAPOLEON-2 study). We previously reported the retrospective data in ASCO-GI 2023, and here we report the final results of the prospective part. Methods: We prospectively collected data of urPC patients treated with NFF who had received at least one previous chemotherapy line in 17 hospitals in Japan from June 2021 to October 2023. The primary endpoint was overall survival (OS). Secondary endpoints were overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), dose intensity (DI) and adverse events (AEs). In addition, OS and PFS among the therapeutic lines of NFF were also analyzed. Results: A total of 150 urPC patients were prospectively enrolled. The median follow-up period was 7.2 months (95% confidence interval [CI], 6.3–8.8); median age, 72 years (range, 45–85), with 81 female patients (54%). The Eastern Cooperative Oncology Group performance status was 0/1/2/3 in 46/93/10/1 patients, respectively. Sixteen patients (11%) had locally advanced disease; 134 (89%) had metastatic disease; 77 (51%) had liver metastasis; and 47 (31%) had peritoneal metastasis. All patients previously received gemcitabine-based therapy. NFF was administered as 2nd/3rd/4th-or-later-line therapy to 87/53/10 patients, respectively. The median OS was 7.8 months (95% CI, 6.6–9.2); median PFS, 3.7 months (95% CI, 2.8–4.9); overall response rate, 11%; and disease control rate, 56%. The relative dose intensity was 72.7% with NAL-IRI and 79.4% with fluorouracil. The initial dose of NAL-IRI was reduced in 84 patients (56%), mainly owing to decreased organ function (17%), followed by age (12%), worsened performance status (10%), or UGT1A1 examination status (5%). Dosage reduction of NAL-IRI during treatment (independent of the initial dose reduction) was performed in 74 patients (49%), mainly owing to neutropenia (22%) and anorexia (11%). Frequent Grade 3/4 adverse events were neutropenia (27%), anorexia (19%), and leukopenia (16%). Grade 5 peritoneal infection was observed in only one patient. The median OS and PFS for NFF in the 2nd-line group, compared with the 3rd-or-later-line group, were 7.4 vs 7.8 months (hazard ratio [HR], 0.97; 95% CI, 0.68–1.39; p=0.88) and 3.3 vs 4.2 months (HR, 1.04; 95% CI, 0.74–1.45; p=0.84), respectively. Conclusions: NFF had appropriate efficacy and manageable toxicity profiles, consistent with our previous report. NFF can be a candidate for 2nd-or-later-line regimens in the real-world. Clinical trial information: UMIN000043939 .