scholarly journals Subgroup analysis by prior non-liposomal irinotecan therapy in NAPOLI-1: a phase 3 study of nal-IRI±5-fluorouracil/leucovorin in patients with metastatic pancreatic ductal adenocarcinoma previously treated with gemcitabine-based therapy

2017 ◽  
Vol 28 ◽  
pp. x67-x68
Author(s):  
J.F. Blanc ◽  
R. Hubner ◽  
C-P Li ◽  
A. Wang-Gillam ◽  
G. Bodoky ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Subgroup Analysis ◽  
Ductal Adenocarcinoma ◽  
Phase 3 ◽  
Previously Treated ◽  
Liposomal Irinotecan

Subgroup analysis by prior lines of metastatic therapy (mtx) in NAPOLI-1: A global, randomized phase 3 study of liposomal irinotecan (nal-IRI) ± 5-fluorouracil and leucovorin (5-FU/LV), vs. 5-FU/LV in patients (pts) with metastatic pancreatic ductal adenocarcinoma (mPDAC) who have progressed following gemcitabine-based therapy.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 4127-4127
Author(s):  
Teresa Mercade Macarulla ◽  
Jens T. Siveke ◽  
Andrea Wang-Gillam ◽  
Chung-Pin Li ◽  
Gyorgy Bodoky ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Subgroup Analysis ◽  
Analysis Data ◽  
Ductal Adenocarcinoma ◽  
Phase 3 ◽  
Study Methodology ◽  
Liposomal Irinotecan ◽  
Grade 3 ◽  
Post Hoc ◽  
Clinical Trial Information

4127 Background: In the NAPOLI-1 study, nal-IRI+5-FU/LV significantly increased median OS vs. 5-FU/LV control (6.1 vs. 4.2 mo; unstratified HR = 0.67 [0.49–0.92]; p = .012). This is a subgroup analysis by prior lines of mtx. Methods: Study methodology has been published (Wang-Gillam; Lancet 2016). This exploratory subgroup analysis compares outcomes in pts with 0–1 vs. ≥2 prior mtx lines, based on primary survival analysis data (cut-off February 2014) of the ITT population. Results: OS, PFS and CA19-9 response rates in pts with 0–1 (65.8% of pts) or ≥2 (34.2%) prior mtx lines are shown (see Table). Median OS for nal-IRI+5-FU/LV improved vs. 5-FU/LV by 2.1 mo to 6.2 mo (HR = 0.66; p = .03) in pts with 0–1 prior mtx lines and by 1.1 mo to 5.4 mo (HR = 0.68; p = .18) in pts with ≥2 prior mtx lines. The safety profile was similar between subgroups with nal-IRI+5-FU/LV (≥grade 3 drug-related AEs: 43 [55%] with 0–1 and 20 [51%] with ≥2 prior mtx lines). Conclusions: This post-hoc subgroup analysis shows significant increases for nal-IRI+5-FU/LV over 5-FU/LV in OS, PFS and CA19-9 response in pts with 0–1 prior mtx lines. Median OS benefit was less prominent in later lines, but conclusions are restricted by limited pt numbers. Clinical trial information: NCT01494506. [Table: see text]

Subgroup analysis by baseline pain intensity (BPI) and analgesic use (BAU) in NAPOLI-1: A phase III study of liposomal irinotecan (nal IRI)±5-fluorouracil/ leucovorin (5-FU/LV) in patients (pts) with metastatic pancreatic ductal adenocarcinoma (mPDAC) previously treated with gemcitabine-based therapy.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 379-379
Author(s):  
Teresa Mercade Macarulla ◽  
Jens T. Siveke ◽  
Andrew Peter Dean ◽  
Richard Hubner ◽  
Jean-Frédéric Blanc ◽  
...  
Keyword(s):  
Subgroup Analysis ◽  
Phase Iii ◽  
Ductal Adenocarcinoma ◽  
Prognostic Effect ◽  
Baseline Pain Intensity ◽  
Phase Iii Study ◽  
Previously Treated ◽  
Recorded Data ◽  
Liposomal Irinotecan ◽  
Post Hoc

379 Background: We report an exploratory, post hoc subgroup analysis in pts with BPI and BAU data receiving nal-IRI+5-FU/LV, nal-IRI or 5-FU/LV in NAPOLI-1 (NCT01494506). In this pivotal trial, nal-IRI+5-FU/LV improved median OS (mOS) vs. 5-FU/LV (6.1 vs. 4.2 mo [HR=0.67; p=0.012]). Methods: BPI/BAU included an average of 3-7 days pt-recorded data before randomisation. Greater values indicated greater pain for BPI using a 100 mm visual analogue scale. BAU was converted to morphine equivalent mg/day. Results: Of 417 ITT pts, 295 had BPI and 299 had BAU data. Mean and median BPI were 28.6 and 25.0, respectively, and BAU were 33.3 and 8.1 mg/day, respectively. The percentage of pts with KPS ≥ 80 was higher in ≤ mean/≤ median (n=159/148) BPI groups vs. > mean/> median (n=136/147) BPI groups (96-97 vs. 83%) and in ≤mean/≤median (n=207/150) BAU groups vs. > mean/> median (n=92/149) BAU groups (95-97 vs. 82-85%). mOS and median PFS (mPFS) were higher for nal-IRI+5-FU/LV vs 5-FU/LV in all groups, with ≤ mean/≤ median BPI or BAU showing better outcomes vs. > mean/> median BPI or BAU (Table). Conclusions: BPI and BAU appear to have a prognostic effect on outcomes in mPDAC pts in the NAPOLI-1 study. No predictive effect was observed, with nal-IRI+5-FU/LV showing higher mOS vs. 5-FU/LV in all groups. Clinical trial information: NCT01494506. [Table: see text]

NAPOLI-3: An open-label, randomized, phase III study of first-line liposomal irinotecan + 5-fluorouracil/leucovorin + oxaliplatin versus nab-paclitaxel + gemcitabine in patients with metastatic pancreatic ductal adenocarcinoma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS4661-TPS4661
Author(s):  
Zev A. Wainberg ◽  
Tanios S. Bekaii-Saab ◽  
Richard Hubner ◽  
Teresa Macarulla ◽  
Andrew Scott Paulson ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Primary Endpoint ◽  
Group Performance ◽  
Phase 1 ◽  
Phase Iii ◽  
Ductal Adenocarcinoma ◽  
First Line ◽  
Open Label ◽  
Phase 3 ◽  
Liposomal Irinotecan

TPS4661 Background: Liposomal irinotecan administered with 5-fluorouracil/leucovorin (5-FU/LV) is approved in the USA for metastatic pancreatic ductal adenocarcinoma (mPDAC) following progression with gemcitabine-based therapy. A phase 1/2 study in previously untreated locally advanced/metastatic PDAC showed promising anti-tumor activity with liposomal irinotecan 50 mg/m2 free base + 5-FU 2400 mg/m2 + LV 400 mg/m2 + oxaliplatin (OX) 60 mg/m2 on days 1 and 15 of a 28-day cycle (Wainberg et al. Ann Oncol 2019;30 Suppl 4: SO-005). Herein, we present the design of the phase 3 NAPOLI-3 study investigating the efficacy and safety of this regimen as first-line therapy in patients with mPDAC. Methods: NAPOLI-3 (NCT04083235) is a phase 3, open-label, randomized, global study in adults with histologically/cytologically confirmed pancreatic adenocarcinoma not previously treated in the metastatic setting. Patients are required to have one or more metastatic tumors measurable with computed tomography/magnetic resonance imaging and an Eastern Cooperative Oncology Group performance status score of 0–1. Site activation began in Dec 2019 and enrollment is ongoing. Random allocation (1:1) of 750 patients is planned to liposomal irinotecan + 5-FU/LV + OX (regimen as per phase 1/2 study) or nab-paclitaxel 125 mg/m2 + gemcitabine 1000 mg/m2 on days 1, 8 and 15 in a 28-day cycle. The primary endpoint is overall survival (OS). Secondary endpoints (progression-free survival [PFS] and overall response rate assessed with Response Evaluation Criteria in Solid Tumors v1.1 criteria) will be compared only if the primary endpoint shows superiority for liposomal irinotecan + 5-FU/ LV + OX over nab-paclitaxel + gemcitabine. Safety assessments include adverse-event monitoring. Patients will continue treatment until disease progression, unacceptable toxicity or study withdrawal, and will then be followed for survival every 2 months until death or study end (when all patients have died, withdrawn consent or are lost to follow-up). Clinical trial information: NCT04083235 .

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

2021 ◽  
Author(s):  
Se Jun Park ◽  
Hyunho Kim ◽  
Kabsoo Shin ◽  
Tae Ho Hong ◽  
Ja Hee Suh ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Adverse Events ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Real World ◽  
Median Overall Survival ◽  
Ductal Adenocarcinoma ◽  
Nanoliposomal Irinotecan ◽  
Previously Treated ◽  
Grade 3

Abstract 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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