Perioperative NALIRIFOX in patients with resectable pancreatic ductal adenocarcinoma: The open-label, multicenter, phase II nITRO trial.

Liposomal irinotecan NALIRIFOX Perioperative treatment Resectable pancreatic ductal adenocarcinoma

Journal

European journal of cancer (Oxford, England : 1990)
ISSN: 1879-0852
Titre abrégé: Eur J Cancer
Pays: England
ID NLM: 9005373

Informations de publication

Date de publication:
11 Nov 2023
Historique:
received: 17 10 2023
accepted: 28 10 2023
medline: 24 11 2023
pubmed: 24 11 2023
entrez: 23 11 2023
Statut: aheadofprint

Résumé

Upfront surgery followed by postoperative treatment is a commonly adopted treatment for resectable pancreatic ductal adenocarcinoma (rPDAC). However, the risk of positive surgical margins, the poor recovery that often impairs postoperative treatments, and the risk of recurrence might limit the outcome of this strategy. This study evaluated the safety and the activity of liposomal irinotecan 50 mg/m Eligible patients had a rPDAC with < 180° interface with major veins' wall. Patients received 3 cycles before and 3 cycles after resection with NALIRIFOX, days 1 and 15 of a 28-day cycle. The primary endpoint was the proportion of patients undergoing an R0 resection. 107 patients began preoperative treatment. Nine patients discontinued the treatment because of related or unrelated adverse events. Disease-control rate was 92.9%. 87 patients underwent surgical exploration, 11 had intraoperative evidence of metastatic disease, and 1 died for surgical complications. R0 resection rate was 65.3%. 49 patients completed the three postoperative cycles. The most common grade ≥ 3 adverse events were diarrhea and neutropenia. Median overall survival (OS) of ITT patients was 32.3 months (95% CI 27.8-44.3). Median disease-free and OS from surgery of resected patients were 19.3 (95% CI 12.6-34.1) and 40.3 months (95% CI 29-NA), respectively. Perioperative NALIRIFOX was manageable and active, and deserves further investigation in randomized trials comparing it with standard upfront surgery followed by adjuvant therapy.

Sections du résumé

BACKGROUND BACKGROUND
Upfront surgery followed by postoperative treatment is a commonly adopted treatment for resectable pancreatic ductal adenocarcinoma (rPDAC). However, the risk of positive surgical margins, the poor recovery that often impairs postoperative treatments, and the risk of recurrence might limit the outcome of this strategy. This study evaluated the safety and the activity of liposomal irinotecan 50 mg/m
METHODS METHODS
Eligible patients had a rPDAC with < 180° interface with major veins' wall. Patients received 3 cycles before and 3 cycles after resection with NALIRIFOX, days 1 and 15 of a 28-day cycle. The primary endpoint was the proportion of patients undergoing an R0 resection.
RESULTS RESULTS
107 patients began preoperative treatment. Nine patients discontinued the treatment because of related or unrelated adverse events. Disease-control rate was 92.9%. 87 patients underwent surgical exploration, 11 had intraoperative evidence of metastatic disease, and 1 died for surgical complications. R0 resection rate was 65.3%. 49 patients completed the three postoperative cycles. The most common grade ≥ 3 adverse events were diarrhea and neutropenia. Median overall survival (OS) of ITT patients was 32.3 months (95% CI 27.8-44.3). Median disease-free and OS from surgery of resected patients were 19.3 (95% CI 12.6-34.1) and 40.3 months (95% CI 29-NA), respectively.
CONCLUSION CONCLUSIONS
Perioperative NALIRIFOX was manageable and active, and deserves further investigation in randomized trials comparing it with standard upfront surgery followed by adjuvant therapy.

Identifiants

pubmed: 37995598
pii: S0959-8049(23)00732-3
doi: 10.1016/j.ejca.2023.113430
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

113430

Informations de copyright

Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Competing Interest DM received honoraria as an advisory board member or consultant from Servier, Incyte, iOnctura, Eli Lilly, Evotec, Baxter; received institutional support for research project from Shire, Celgene, Incyte, iOnctura, Roche. GM received honoraria as consultant from Oncosil, and institutional support for research project from Fibrogen. MDO received honoraria as an advisory board member or consultant from Bracco Diagnostics, Siemens Healthcare Diagnostic, Hitachi, Novartis. RdR received honoraria as an advisory board member or consultant from Bracco Diagnostics and Fujifilm. AS received honoraria as an advisory board member or consultant from Incyte, MSD, Amgen, GlaxoSmithkline. All other authors have declared no conflicts of interest.

Auteurs

Davide Melisi (D)

Investigational Cancer Therapeutics Clinical Unit, Azinda Ospedaliera Integrata, Verona, Italy; Digestive Molecular Clinical Oncology Research Unit, University of Verona, Verona, Italy. Electronic address: davide.melisi@univr.it.

Camilla Zecchetto (C)

Medical Oncology Unit, Azinda Ospedaliera Integrata, Verona, Italy; Digestive Molecular Clinical Oncology Research Unit, University of Verona, Verona, Italy.

Valeria Merz (V)

Digestive Molecular Clinical Oncology Research Unit, University of Verona, Verona, Italy.

Giuseppe Malleo (G)

Pancreatic Surgery Unit, Azinda Ospedaliera Integrata, Verona, Italy.

Luca Landoni (L)

Pancreatic Surgery Unit, Azinda Ospedaliera Integrata, Verona, Italy.

Alberto Quinzii (A)

Medical Oncology Unit, Azinda Ospedaliera Integrata, Verona, Italy; Digestive Molecular Clinical Oncology Research Unit, University of Verona, Verona, Italy.

Simona Casalino (S)

Digestive Molecular Clinical Oncology Research Unit, University of Verona, Verona, Italy.

Federica Fazzini (F)

Investigational Cancer Therapeutics Clinical Unit, Azinda Ospedaliera Integrata, Verona, Italy.

Marina Gaule (M)

Medical Oncology Unit, Azinda Ospedaliera Integrata, Verona, Italy.

Camilla Pesoni (C)

Medical Oncology Unit, Azinda Ospedaliera Integrata, Verona, Italy.

Luca Casetti (L)

Pancreatic Surgery Unit, Azinda Ospedaliera Integrata, Verona, Italy.

Alessandro Esposito (A)

Pancreatic Surgery Unit, Azinda Ospedaliera Integrata, Verona, Italy.

Giovanni Marchegiani (G)

Investigational Cancer Therapeutics Clinical Unit, Azinda Ospedaliera Integrata, Verona, Italy; Hepatopancreatobiliary and Liver Transplant Surgery Unit, University of Padua, Padua, Italy.

Cristiana Piazzola (C)

Centro Ricerche Cliniche, Azinda Ospedaliera Integrata, Verona, Italy.

Mirko D'Onofrio (M)

Radiology Unit, Azinda Ospedaliera Integrata, Verona, Italy.

Riccardo de Robertis (R)

Radiology Unit, Azinda Ospedaliera Integrata, Verona, Italy.

Armando Gabbrielli (A)

Digestive Endoscopy Unit, Azinda Ospedaliera Integrata, Verona, Italy.

Laura Bernardoni (L)

Digestive Endoscopy Unit, Azinda Ospedaliera Integrata, Verona, Italy.

Stefano F Crino (SF)

Digestive Endoscopy Unit, Azinda Ospedaliera Integrata, Verona, Italy.

Silvia Pietrobono (S)

Digestive Molecular Clinical Oncology Research Unit, University of Verona, Verona, Italy.

Claudio Luchini (C)

Pathology Unit, Azienda Ospedaliera Universitaria Integrata, Azinda Ospedaliera Integrata, Verona, Italy.

Camillo Aliberti (C)

Radiology Unit, Azinda Ospedaliera Integrata, Verona, Italy.

Guido Martignoni (G)

Pathology Unit, Azinda Ospedaliera Integrata, Verona, Italy.

Stefano Milleri (S)

Centro Ricerche Cliniche, Azinda Ospedaliera Integrata, Verona, Italy.

Giovanni Butturini (G)

Pancreatic Surgery Unit, Ospedale Pederzoli, Peschiera del Garda, Italy.

Aldo Scarpa (A)

Pathology Unit, Azienda Ospedaliera Universitaria Integrata, Azinda Ospedaliera Integrata, Verona, Italy.

Roberto Salvia (R)

Pancreatic Surgery Unit, Azinda Ospedaliera Integrata, Verona, Italy.

Claudio Bassi (C)

Pancreatic Surgery Unit, Azinda Ospedaliera Integrata, Verona, Italy.

Classifications MeSH