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A multicenter observational study of liposomal irinotecan and fluorouracil/leucovorin in patients with unresectable or recurrent pancreatic cancer (NAPOLEON-2): Retrospective part
Background
Nanoliposomal irinotecan and fluorouracil with folinic acid (NAL-IRI/FU/LV) is the standard regimen after gemcitabine-based therapy for unresectable or recurrent pancreatic cancer (urPC), based on the results of a phase 3 trial, NAPOLI-1 study. However, the efficacy and toxicity of NAL-IRI/FU/LV in the clinical setting remain unclear. Therefore, we conducted this NAPOLEON-2 study to investigate the clinical features of NAL-IRI/FU/LV and explore the predictive and prognostic factors, both retrospectively and prospectively. Here we show the efficacy and toxicity of NAL-IRI/FU/LV of the retrospective part.
Methods
This retrospective study collected data from urPC patients treated with NAL-IRI/FU/LV, who had received at least one previous chemotherapy, from 21 hospitals in Japan during the period from June 2020 to May 2021. Patient characteristics, treatment efficacy, and adverse events were analyzed. Overall survival (OS) and progression-free survival (PFS) were estimated by Kaplan-Meier analysis. Incidentally, OS and PFS among the therapeutic lines of NAL-IRI/FU/LV were also analyzed.
Results
NAL-IRI/FU/LV was administered to 161 patients. The median follow-up period was 5.3 months (95% confidence interval [95%CI], 4.7–6.3). All patients had previous gemcitabine-based therapy, and NAL-IRI/FU/LV was administered as 2nd/3rd/4th-line chemotherapy to 104/41/16 patients, respectively. Eighteen patients (11%) had received previous irinotecan. The median age was 67 (range, 38–85), and 88 males (55%) were included. Performance Status (PS) was 0/1/2/3 in 46/47/6/1 patients. Nineteen patients (12%) had locally advanced disease and 142 (88%) patients had metastatic disease. Eighty-nine patients (55%) had liver metastasis and 44 patients (27%) had peritoneal metastasis. The median treatment courses were 5 (range, 1–29). The median OS was 9.5 months (95%CI, 7.5–11.0). The median PFS was 3.3 months (95%CI, 2.8–4.4). The overall response rate was 5%, and the disease control rate was 52%. The relative dose intensity was 82.8% in NAL-IRI and 98.2% in FU. The initial dose of NAL-IRI was reduced in 57 patients (35%), mainly because of the uridine diphosphate glucuronosyltransferase (UGT) 1A1 examination status (8%), followed by organ function decrease (6%). Dosage reduction during the treatment (independent from the initial dosage reduction) was conducted in 63 patients (39%), mainly because of neutropenia (14%) and anorexia (10%). More frequent grade 3/4 adverse events (AEs) were neutropenia (23%), anorexia (12%), leukopenia (12%), and anemia (9%). No Grade 5 AE was observed. The median OS in NAL-IRI/FU/LV as 2nd-line therapy compared by as 3rd-line or later regimen was 9.1 vs 10.7 months (hazard ratio [HR], 0.69; 95% CI, 0.42–1.13; p=0.14). The median PFS in NAL-IRI/FU/LV as 2nd-line therapy compared to as 3rd-line or later regimen was 2.9 vs 4.2 months (HR, 0.90; 95% CI, 0.63–1.29; p=0.58).
Conclusions
NAL-IRI/FU/LV presented appropriate efficacy compared to previous studies, and the one on OS was shown regardless of therapeutic lines. Toxicity profiles were similar to them and thought to be manageable. In conclusion, NAL-IRI/FU/LV could be a candidate for 2nd-line or later regimen in the real world.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosures
A. Hosokawa: Honoraria (self): Yakult Honsha, Taiho Pharmaceutical, Daiichi Sankyo, Chugai Pharma, Ono Pharmaceutical, Eisai, Lilly; Research grant / Funding (institution): Chugai Pharma, Taiho Pharmaceutical, Ono Pharmaceutical. All other authors have declared no conflicts of interest.
