Dataset Information

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

ABSTRACT:

Introduction

This multicenter, real-world cohort study aimed to evaluate the effectiveness of early cumulative dose administration and dosing pattern of liposomal irinotecan plus fluorouracil/leucovorin (nal-IRI+5-FU/LV) in patients with gemcitabine-refractory metastatic pancreatic ductal adenocarcinoma (mPDAC).

Material and methods

The electronic medical records of mPDAC patients treated with nal-IRI+5-FU/LV in nine participating centers were manually reviewed. To accommodate to the NAPOLI-1 study population, only patients with an Eastern Cooperative Oncology Group Performance Score of 0-1 were included. The survival impact of the relative 6-week cumulative dose and dosing pattern (standard vs. reduced starting dose, with and without further dose modification) were investigated.

Results

Of the 473 included patients, their median overall survival (mOS) was 6.8 [95% CI, 6.2-7.7] months. The mOS of patients who received a relative 6-week cumulative dose of >80%, 60%-80%, and <60% were 7.9, 8.2, and 4.3 months, respectively (p<0.0001). Their survival impact remained significant after covariate adjustment using Cox regression. The mOS was 8.0-8.2 months in patients with a standard starting dose with and without early dose modification, and 9.3 and 6.7 months in those who had a reduced starting dose with and without escalation in the subsequent treatment, respectively. The incidence of grade 3-4 neutropenia and diarrhea was 23.3% and 2.7%, respectively.

Conclusion

Our results support the use of nal-IRI+5-FU/LV in gemcitabine-refractory mPDAC and suggest that a lower starting dose followed by a re-escalation strategy could achieve clinical outcomes comparable to those with standard starting doses in real-world practice.

SUBMITTER: Su YY

PROVIDER: S-EPMC9256928 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundThe efficacy of combination chemotherapy beyond the first-line setting remains modest in patients with advanced pancreatic adenocarcinoma (PAC). Evidence from recent clinical studies has shown that liposomal irinotecan (nal-IRI) plus 5-fluorouracil (5-FU) and leucovorin (LV) resulted in survival benefits in patients with advanced pancreatic adenocarcinoma (APAC) after progression on gemcitabine-based treatment. However, the survival benefits of nal-IRI in the third and later lines, in which limited options are available, have yet to be extensively studied. Also, some studies have shown conflicting results regarding the impact of prior treatment with conventional IRI on patient outcomes following treatment with nal-IRI. Therefore, this real-world study aimed to evaluate the efficacy and safety of nal-IRI plus 5FU-LV in advanced PAC patients who progressed on conventional IRI-containing regimens.MethodsA retrospective chart review was conducted between November 2016 to December 2022 on 30 patients diagnosed with advanced PAC who completed at least one cycle of nal-IRI plus 5-FU- LV and were previously treated with conventional IRI. Data regarding survival outcomes were retrieved.ResultsThirty patients met the inclusion criteria. Overall, 76.7% of the patients received at least two lines of therapy prior to nal-IRI. The median overall duration of nal-IRI treatment was 2.0 months (IQR: 1.3 - 3.9 months). One patient (3.3%) had a partial response, and seven patients (23.3%) had stable disease as their best response. The median progression-free survival (PFS) was 1.9 months (95% CI 1.6 - 2.0) and the 6-month PFS rate was 20.0%. The median overall survival (OS) was 5.0 months (95% CI 3.4 - 7.0), and the 6-month OS rate was 36.7%. An interval between conventional IRI and nal-IRI ≥5.5 months was significantly associated with prolonged OS of 10.2 months (95% CI 3.3 - 12.1) versus 4.3 months (95% CI 2.1 - 5.9; p =0.003). Ten patients (33.3%) experienced grade 3 adverse events, most commonly nausea, fatigue, diarrhea, and non-neutropenic fever.ConclusionNal-IRI plus 5FU/LV had modest survival benefits and an acceptable safety profile in patients with prior conventional IRI. A longer interval between conventional IRI and nal-IRI was associated with increased survival outcomes.

Project description:BackgroundCurrently, nanoliposomal irinotecan (nal-IRI) + 5-fluorouracil/folinic acid (5-FU/LV) is the only approved second-line treatment for patients suffering from metastatic pancreatic ductal adenocarcinoma (mPDAC). However, also other chemotherapeutic regimens are used in this setting and due to the lack of clear real-world data on the efficacy of the different regimens, there is no consensus on the optimal treatment sequence for mPDAC patients.ObjectivesTo provide information on the safe and efficacious use of nal-IRI + 5-FU/LV in clinical practice in Belgium, which is needed for healthcare professionals to estimate the risk-benefit ratio of the intervention.MethodsMedical data of adult patients with mPDAC who were treated with nal-IRI + 5-FU/LV in one of the participating Belgian hospitals were retrospectively collected. Kaplan-Meier analysis was performed to obtain survival curves to estimate the median overall survival (OS) and progression-free survival (PFS). All other results were presented descriptively.ResultsA total of 56 patients [median age at diagnosis: 69 years (range 43 years), 57.1% male] were included. Patients received a median of 5 (range 49 cycles) nal-IRI + 5-FU/LV cycles, extended over 10 weeks (range 130.8 weeks). The median start dose for nal-IRI was 70 mg/m² (range 49.24 mg/m²) and chemotherapy dose reduction and delay occurred in, respectively, 42.8% and 37.5% of the patients. The median OS was 6.8 months (95% CI: 5.6-8.4 months) with a 6-month survival rate of 57.4% and a 1-year survival rate of 27.8% in the overall study population. The median OS for patients treated with nal-IRI as second-line therapy or as later-line treatment was, respectively, 6.8 months (95% CI: 5.9-7.0 months) and 5.6 months (95% CI: 4.2-no upper limit). In the overall study population, a median PFS of 3.1 months (95% CI: 2.4-4.6 months) and a disease control rate of 48.3%, comprising 30.4% stable disease, 16.1% partial and 1.8% complete response, was observed. The median PFS for patients treated with nal-IRI as second-line therapy was 3.9 months (95% CI: 2.8-4.8 months) while this was 2.4 months (95% CI: 1.9-9.1 months) for those that received nal-IRI in a later-line treatment. In terms of safety, gastrointestinal problems occurred most (64.3% of the patients) and from all reported treatment emergent adverse events, 39.2% were grade 3 or 4.ConclusionNal-IRI + 5-FU/LV is a valuable, effective, and safe sequential treatment option following gemcitabine-based therapy in patients with mPDAC.Trial detailsRetrospective study on the efficacy and tolerability of liposomal irinotecan (NALIRI); ClinicalTrials.gov Identifier: NCT0509506 (https://clinicaltrials.gov/ct2/show/NCT05095064?term=naliri&draw=2&rank=2).