Impact of dose reduction or dose delay on the efficacy of liposomal irinotecan (nal-IRI)+5-fluorouracil/leucovorin (5-FU/LV): Survival analysis from NAPOLI-1

Chen, L.-T.; Macarulla, Teresa; Blanc, Jean‐Frédéric; Mirakhur, Beloo; Jong, Floris A. de; Belanger, Bruce; Bekaii‐Saab, Tanios; Siveke, Jens T.

doi:10.1093/annonc/mdy282.117

Cited by 6 publications

(9 citation statements)

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“…With respect to dose modi cation, 33 (64.7%) of 51 patients experienced dose modi cation (dose reduction, n = 30; dose delay, n = 13) during the rst 6weeks. These ndings were consistent with the results that 50 (60%) of 93 patients treated with modi ed dose during the rst 6 weeks in the NAPOLI-I study [15]. Reduced RDI was expected to be associated with poor survival outcomes 13 , but in the current study, reduced RDI was not signi cantly associated with clinical outcomes which is consistent with other previous studies [14,15].…”

Section: Discussionsupporting

confidence: 92%

“…These ndings were consistent with the results that 50 (60%) of 93 patients treated with modi ed dose during the rst 6 weeks in the NAPOLI-I study [15]. Reduced RDI was expected to be associated with poor survival outcomes 13 , but in the current study, reduced RDI was not signi cantly associated with clinical outcomes which is consistent with other previous studies [14,15]. Rather, patients with reduced RDI showed longer PFS, probably because patients who had been treated for a long period of time received more frequent modi ed dose of chemotherapy.…”

Section: Discussionsupporting

confidence: 91%

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The Role of Nanoliposomal Irinotecan Plus Fluorouracil and Folinic Acid as Second-Line Treatment Option in Patients With Metastatic Pancreatic Ductal Adenocarcinoma

Park

Kim

Shin

et al. 2021

Preprint

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BackgroundAccording to the NAPOLI-1 trial, nanoliposomal irinotecan (nal-IRI) plus 5-fluorouracil/leucovorin (5-FU/LV) showed improved overall survival compared to fluorouracil alone for patients with metastatic pancreatic cancer who previously treated gemcitabine-based therapy. In that trial, Asian patients had frequent dose modification due to hematological toxicity. There has been limited information on the clinical benefit and toxicity of this regimen in a real-world setting. Herein, we assessed real-world experience of nal-IRI plus 5-FU/LV in patients with advanced pancreatic cancer after gemcitabine failure.MethodsWe conducted a single institution retrospective analysis of response, survival and safety in patients who had been treated with nal-IRI with 5-FU/LV. Patients with metastatic pancreatic ductal adenocarcinoma previously treated with gemcitabine-based therapy received nal-IRI (80mg/m2) with 5-FU/LV every 2 weeks. ResultsFifty-one patients received nal-IRI plus 5-FU/LV between January 2015 and December 2020. The median age was 67 years, and males were 58.8%. A total of 40 (78.4%) and 11 (21.6%) patients had received one and two lines of prior chemotherapy before enrollment, respectively. Median progression-free survival was 2.8 months (95% confidence interval [CI] 1.8-3.7) and median overall survival was 7.0 months (95% CI 6.0-7.9). Chemotherapy doses were reduced or delayed in 33 (64.7%) patients during the first 6 weeks and median relative dose intensity was 0.87. Thirty-six (70.6%) patients experienced any grade 3 or 4 adverse events. Most common grade 3 or 4 adverse event was neutropenia (58.8%) and most non-hematologic adverse events were under grade 2. Since the start of first-line chemotherapy, median overall survival was 16.3 months (95% CI 14.1-18.4).ConclusionsNal-IRI plus 5-FU/LV seems to be effective, with manageable toxicities, after gemcitabine-based treatment in patients with metastatic pancreatic ductal adenocarcinoma. Trial registration Retrospectively registered

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 91%

The Role of Nanoliposomal Irinotecan Plus Fluorouracil and Folinic Acid as Second-Line Treatment Option in Patients With Metastatic Pancreatic Ductal Adenocarcinoma

Park

Kim

Shin

et al. 2021

Preprint

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“…Despite inherent differences between clinical trials and real-world studies, OS in the overall study population in the present analysis was consistent with that reported in NAPOLI-1 (4.2 months [95% CI: 3.3-5.3] vs 6.2 months [95% CI: 4.8-8.4], respectively) [13]. Similarly, the impact of dose reduction was consistent with real-world findings; post hoc analyses of NAPOLI-1 data determined a median OS of 9.4 and 8.4 months in patients who required tolerability-guided dose reduction or delay, respectively [14]. The present real-world study confirms the safety profile of liposomal irinotecan + 5-FU/LV seen in clinical trials.…”

Section: Discussionsupporting

confidence: 61%

“…The recommended dose of liposomal irinotecan is 70 mg/m 2 free base, administered as part of the liposomal irinotecan + 5-FU/LV regimen [11]. However, post hoc analyses of data from NAPOLI-1 suggest that dose reductions or delays to manage toxicities do not have an adverse impact on outcomes [14]. This finding is supported by data from two small-scale, real-world studies: dose reductions were not associated with decreases in OS or PFS in retrospective real-world studies in patients with advanced PDAC in the USA (n = 56) and Austria (n = 52) [15,16].…”

mentioning

confidence: 99%

Real-World Outcomes Associated with Liposomal Irinotecan Dose Reductions in Metastatic Pancreatic Ductal Adenocarcinoma

Kim

Surinach²,

Corvino³

et al. 2020

Future Oncol.

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Aim: This study sought to understand the association between liposomal irinotecan dose reductions (DRs) and clinical outcomes among patients with metastatic pancreatic ductal adenocarcinoma. Materials & methods: A retrospective study of adult patients with metastatic pancreatic ductal adenocarcinoma treated with liposomal irinotecan in the Flatiron Health database was conducted to assess treatment and clinical outcomes. Results: DRs occurred in 28.4% of the 320 patients in the study. Patients with DRs had longer overall survival (7.7 [95% CI: 6.2–10.2]) vs 3.6 [3.2–4.1] months) and time to discontinuation (4.2 [3.0–4.9] vs 1.4 [1.0–1.5] months) than patients without DRs. Results were consistent in a validation analysis requiring three cycles of treatment. Conclusion: Liposomal irinotecan DRs were associated with improved clinical outcomes compared with patients without DRs.

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“…In addition, dose modifications (delays or reductions) were reported in a higher percentage of patients ≥75 years versus younger patients and it is possible that this also had an impact on the incidence of adverse events in this subgroup. A recent post-hoc analysis suggested that dose modification had no significant impact on survival outcomes in the overall NAPOLI-1 population [23]. In the current subgroup analysis, older age groups had numerically lower median OS versus younger patients but no trend in median PFS was observed.…”

Section: Discussionmentioning

confidence: 48%

Liposomal irinotecan and 5-fluorouracil/leucovorin in older patients with metastatic pancreatic cancer – A subgroup analysis of the pivotal NAPOLI-1 trial

Macarulla

Blanc

Wang‐Gillam

et al. 2019

Journal of Geriatric Oncology

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Objectives: Pancreatic cancer is a highly lethal disease predominantly affecting older patients. Characterization of outcomes in these patients may help optimise treatment decisions. The global, phase 3 NAPOLI-1 trial (NCT01494506) demonstrated an overall survival (OS) benefit with liposomal irinotecan and 5-flurouracil/ leucovorin (nal-IRI + 5-FU/LV) versus 5-FU/LV. This subgroup analysis explored impact of age on outcomes in NAPOLI-1 patients, and nal-IRI + 5-FU/LV efficacy and safety in older patients. Materials and Methods: This exploratory, post-hoc analysis of the NAPOLI-1 trial included patients aged ≥eighteen years (no upper limit) with metastatic pancreatic adenocarcinoma that had progressed on gemcitabine-based therapy. Patients were stratified by age (cut-offs at 65, 70, and 75 years); OS and progression-free survival (PFS) were estimated by Kaplan-Meier analysis. Results: Of 417 randomized patients, 192 (46%), 110 (26%) and 43 (10%) were aged ≥65, ≥70 and ≥ 75 years, respectively. Mortality risk and risk of disease progression were similar in older and younger patients independent of treatment (HRs for median [m]OS/mPFS comparisons were 0.88/0.95 [b65 versus ≥65 years], 0.89/0.88 [b70 versus ≥70 years] and 1.04/0.98 [b75 versus ≥75 years]; P N .25). Reduced mortality/morbidity risk with nal-IRI + 5-FU/LV in older subgroups was in line with the wider population. No additional toxicities with nal-IRI + 5-FU/LV were observed in older patients: 86% of patients ≥75 years versus 69% b75 years required a dose delay or reduction due to toxicities (43% versus 32% dose reductions). Discussion: Results suggest that older patients with metastatic pancreatic adenocarcinoma that progressed on prior gemcitabine-based treatment can benefit from second-line therapy, supporting nal-IRI + 5-FU/LV treatment in older patients.

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Impact of dose reduction or dose delay on the efficacy of liposomal irinotecan (nal-IRI)+5-fluorouracil/leucovorin (5-FU/LV): Survival analysis from NAPOLI-1

Cited by 6 publications

References 0 publications

The Role of Nanoliposomal Irinotecan Plus Fluorouracil and Folinic Acid as Second-Line Treatment Option in Patients With Metastatic Pancreatic Ductal Adenocarcinoma

The Role of Nanoliposomal Irinotecan Plus Fluorouracil and Folinic Acid as Second-Line Treatment Option in Patients With Metastatic Pancreatic Ductal Adenocarcinoma

Real-World Outcomes Associated with Liposomal Irinotecan Dose Reductions in Metastatic Pancreatic Ductal Adenocarcinoma

Liposomal irinotecan and 5-fluorouracil/leucovorin in older patients with metastatic pancreatic cancer – A subgroup analysis of the pivotal NAPOLI-1 trial

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