A real-world analysis of nanoliposomal-irinotecan with 5-fluorouracil and folinic acid as third- or later-line therapy in patients with metastatic pancreatic adenocarcinoma

Abstract

Background: Nanoliposomal encapsulation of irinotecan (nal-IRI) with 5-fluorouracil and leucovorin (5-FU/LV) has shown a survival benefit for gemcitabine-pretreated patients with metastatic pancreatic adenocarcinoma (mPAC). The aim of this study was to evaluate the effectiveness and safety of nal-IRI with 5-FU/LV for use beyond second-line treatment after standard frontline therapy for mPAC. Method: This multicenter, retrospective, non-comparative observational study included mPAC patients who received nal-IRI plus 5-FU/LV as third- or later-line therapy after disease progression on first-line FOLFIRINOX (FFX) or gemcitabine plus nab-paclitaxel. Results: In all, 128 patients who received nal-IRI plus 5-FU/LV beyond second-line treatment between October 2017 and July 2021 were analyzed. Most patients (82%) received nal-IRI plus 5-FU/LV as a third-line treatment. The median overall survival (OS) was 4.9 months and the median progression-free survival (PFS) was 2.4 months. Patients with better Eastern Cooperative Oncology Group (ECOG) performance status experienced significantly longer OS (ECOG 0, 8.7 months; ECOG 1, 4.8 months; ECOG 2, 2.9 months; p < 0.001) and PFS (3.9 months; 2.1 months; 1.5 months; p = 0.019). Patients who had not been previously treated with FFX or had a time to progression of 7 months or more on FFX experienced longer OS and PFS than those who did not (6.1 months and 5.6 versus 4.1 months, p = 0.053; 3.6 months and 2.4 versus 2.1 months, p = 0.002). The most common adverse events were neutropenia (56%) and anemia (51%). Conclusion: Our real-world data indicated that nal-IRI plus 5-FU/LV can be effective not only as second-line therapy, but also as third-line or later-line treatment in selected patients. Nal-IRI plus 5-FU/LV may be particularly beneficial for the survival of patients that maintain good general condition or those with favorable prior experience to irinotecan.

The role of nanoliposomal irinotecan plus fluorouracil/leucovorin in the continuum of care of patients with metastatic pancreatic ductal adenocarcinoma

“…The efficacy of 5‐FU/LV‐nal‐IRI was thus reproducible in 11 different centers across Italy and in a less favorably selected population: our cohort was older (age range: 30–83 vs. 57–70 years) and had worse general conditions (ECOG PS ≥1: 56% vs. 41%) than the pivotal trial 12,13 . Six‐ and 12‐month PFS and OS rates were in line with both the NAPOLI‐1 trial 12,13 and real‐world analyses 15–21 . With respect to prior treatment, only 55% of patients in the NAPOLI‐1 trial received Gem combination treatment, 12,13 but most patients (79%) in our study were treated with Gem‐NabP as first‐line.…”

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.…”

Efficacy and tolerance of LV5FU2-carboplatin chemotherapy in patients with advanced pancreatic ductal adenocarcinoma after failure of standard regimens

“…The clinical deterioration and poor prognosis of refractory patients greatly limit the number of candidates for further-line treatment. 31 – 36 Nevertheless, the availability of more effective standard first- and second-line chemotherapies (i.e. FOLFIRINOX and nab-paclitaxel in first line, NALIRI after gemcitabine-based first-line chemotherapy) and improvements in supportive care during the last decade have improved OS of PDAC patients, thus progressively increasing the number of patients who are eligible for further-line treatments.…”