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

Kenneth H Yu,Ethan Burns,Andrew E Hendifar,Mei Sheng Duh,Maen Abdelrahim,Olatunji B Alese,Amber Draper,Gazala Khan,Nathan Bahary,Maral Dersarkissian,Paul Cockrum,Rachel H Bhak,Catherine Nguyen

doi:10.3389/fonc.2021.678070

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.

Highlights

Despite recent diagnostic and therapeutic advances, pancreatic cancer remains an aggressive and difficult to treat malignancy
Patients were treated with liposomal irinotecan in the 1L (17%), 2L (42%), or 3L+ (42%) of the metastatic setting
Among patients treated with liposomal irinotecan in 3L+, 57.0% were treated with a 5-FU-based regimen and 41.7% were treated with a gemcitabine-based regimen in 1L setting; 53.2% were treated with a gemcitabine-based regimen and 34.6% were treated with a 5-FU-based regimen in 2L setting

Summary

Introduction

Despite recent diagnostic and therapeutic advances, pancreatic cancer remains an aggressive and difficult to treat malignancy. In October 2015, the Food and Drug Administration (FDA) approved liposomal irinotecan in combination with 5fluorouracil (5-FU) and leucovorin (LV) for the treatment of metastatic pancreatic ductal adenocarcinoma (mPDAC) in patients that had previously progressed on gemcitabine-based chemotherapy following the results of the pivotal NAPOLI-1 trial. The NAPOLI-1 trial evaluated liposomal irinotecan in combination with 5-FU/LV compared to treatment with 5-FU/ LV alone in patients with mPDAC previously treated with gemcitabine-based therapy [3]. The 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

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Discussion

Conclusion