Clinical Outcomes Among Patients With Metastatic Pancreatic Ductal Adenocarcinoma Treated With Liposomal Irinotecan

Abstract

BackgroundThe NAPOLI-1 trial demonstrated that liposomal irinotecan in combination with fluorouracil (5-FU) and leucovorin (LV) prolonged survival with a manageable safety profile in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) previously treated with gemcitabine-based therapy. Real-world data on clinical outcomes associated with liposomal irinotecan in NAPOLI-1-based regimens is needed to further substantiate this.MethodsThis real-world, retrospective chart review study included patients with mPDAC who received NAPOLI-1-based regimens from six academic centers in the United States. Liposomal irinotecan initiation defined the index date. Overall survival (OS) and progression-free survival (PFS) were assessed with Kaplan-Meier methodology.ResultsThere were 374 patients evaluated; median age was 68 years, and 51% were female. Among 326 patients with baseline ECOG information, approximately 74% had ECOG score <2. Liposomal irinotecan was administered as a doublet with 5-FU in a NAPOLI-1-based regimen in the first line (1L; 16%), 2L (42%), and 3L+ (42%) of the metastatic setting. For patients treated in 1L, 2L, and 3L+, median [95% confidence interval (CI)] OS was 8.0 [5.1, 11.2], 7.3 [5.3, 8.8], and 4.6 [4.0, 5.7] months, and median [95% CI] PFS was 4.2 [2.2, 6.6], 3.0 [2.6, 3.7], and 2.0 [1.7, 2.2] months, respectively.ConclusionsPatients in a real-world setting treated with NAPOLI-1-based liposomal irinotecan doublet regimens at academic centers were older with poorer performance status compared to trial patients yet had similar outcomes and efficacy. Furthermore, liposomal irinotecan was frequently used in the 3L+ setting where no treatment has been approved and provided clinical benefit.

Nanoliposomal irinotecan with fluorouracil and folinic acid in patients with unresectable or recurrent pancreatic cancer: A multicenter retorospective ovservational study (NAPOLEON-2)

“…The proportions of patients with prior 5-FU and platinum were also lower, but there was no signi cant difference when compared with other clinical trials [13]. In addition, there was no signi cant difference in patient backgrounds compared to other real-world clinical observational studies [19][20][21][22][23][24][25][26][27][28][29][30]. Therefore, our study cohort is reasonable and similar with those in previous reports.…”

“…The safety pro le of NFF in the current study appears acceptable in comparison with that in previous reports [19][20][21][22][23][24][25][26][27][28][29][30]. The incidence rates of grade 3 or 4 AEs were < 30%.…”

“…The mOS was 8.1 months, longer than that of the NAPOLI-1 study (median, 6.1 months) and of many retrospective and prospective studies [19][20][21][22][23][24][25][26][27][28][29][30]. This can be attributed to several reasons.…”

“…In this aspect, approximately 40% of patients in the current study underwent dose reductions to reduce AEs. Dose reductions reportedly does not impact survival [22,25], suggesting that appropriate dose modi cations should be considered for longer-term continuation of treatment. We will also report the sub-analysis data on the RDI and dose modi cation in the future.…”

Dosing Pattern and Early Cumulative Dose of Liposomal Irinotecan in Metastatic Pancreatic Cancer: A Real-World Multicenter Study

“…Both the European Medicines Agency and the US Food and Drug Administration have adopted real-world evidence in the regulatory process (7,8). The results of 11 real-world data (RWD) on the effectiveness of nal-IRI+5-FU/ LV in pancreatic cancer from different regions and ethnicities are summarized in Supplementary Table 1 (9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19). However, due to the heterogeneity of study populations, that is, 0%-27.3% of patients with Eastern Cooperative Oncology Group performance score (ECOG PS) ≥2 and 0%-69.6% with a reduced starting dose, these clinical outcomes may not be directly compared (20).…”