Lanreotide as maintenance therapy after first-line treatment in patients with non-resectable duodeno-pancreatic neuroendocrine tumours: An international double-blind, placebo-controlled randomised phase II trial - Prodige 31 REMINET: An FFCD study.


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 2022
Historique:
received: 24 03 2022
revised: 18 07 2022
accepted: 29 07 2022
pubmed: 11 9 2022
medline: 19 10 2022
entrez: 10 9 2022
Statut: ppublish

Résumé

Following European guidelines, patients with aggressive metastatic or locally advanced, non-resectable, duodeno-pancreatic (DP) neuroendocrine tumours (NETs) should receive systemic combination chemotherapy until progression. Aggressive disease is defined as progressive and/or symptomatic metastases with or without significant hepatic invasion (>30-50%), and/or bone metastases. This academic randomised, double-blind, placebo-controlled phase II study aims to evaluate lanreotide autogel 120 mg (LAN) as maintenance treatment after at least 2 months of first-line treatment (L1) in aggressive G1-G2 DP-NET. Patients were randomly assigned in a 1:1 ratio to receive LAN or placebo (PBO), every 28 days, until progression or toxicity. The primary end-point was progression-free survival (PFS) at 6 months. Among the 118 planned patients, 53 were included. Of these, 81.1% had a G2 tumour, and 90.6% had metastatic disease. L1 therapy consisted of chemotherapy (96.8%). Median duration of L1 was 4.6 months (range: 2.0-7.7). At the time of randomisation, 81.1% of patients had stable disease. Median follow-up was 27.0 months (95% CI: 19.5; 31.2). PFS at 6 months was 73.1% (90% CI: 55.3; 86.6) in LAN versus 54.2% (90% CI: 35.8; 71.8) in PBO. Median PFS was 19.4 months (95% CI: 7.6; 32.6) and 7.6 months (95% CI: 3.0; 9.0), respectively. Median overall survival was 41.9 months in PBO and was not reached in LAN. The toxicity profile was mainly grade 1-2 expected toxicities. The encouraging results of lanreotide autogel 120 mg as a maintenance treatment after L1 in aggressive G1/2 DP-NET should be confirmed. NCT02288377 (clinicaltrials.gov).

Sections du résumé

BACKGROUND
Following European guidelines, patients with aggressive metastatic or locally advanced, non-resectable, duodeno-pancreatic (DP) neuroendocrine tumours (NETs) should receive systemic combination chemotherapy until progression. Aggressive disease is defined as progressive and/or symptomatic metastases with or without significant hepatic invasion (>30-50%), and/or bone metastases.
METHODS
This academic randomised, double-blind, placebo-controlled phase II study aims to evaluate lanreotide autogel 120 mg (LAN) as maintenance treatment after at least 2 months of first-line treatment (L1) in aggressive G1-G2 DP-NET. Patients were randomly assigned in a 1:1 ratio to receive LAN or placebo (PBO), every 28 days, until progression or toxicity. The primary end-point was progression-free survival (PFS) at 6 months.
RESULTS
Among the 118 planned patients, 53 were included. Of these, 81.1% had a G2 tumour, and 90.6% had metastatic disease. L1 therapy consisted of chemotherapy (96.8%). Median duration of L1 was 4.6 months (range: 2.0-7.7). At the time of randomisation, 81.1% of patients had stable disease. Median follow-up was 27.0 months (95% CI: 19.5; 31.2). PFS at 6 months was 73.1% (90% CI: 55.3; 86.6) in LAN versus 54.2% (90% CI: 35.8; 71.8) in PBO. Median PFS was 19.4 months (95% CI: 7.6; 32.6) and 7.6 months (95% CI: 3.0; 9.0), respectively. Median overall survival was 41.9 months in PBO and was not reached in LAN. The toxicity profile was mainly grade 1-2 expected toxicities.
CONCLUSIONS
The encouraging results of lanreotide autogel 120 mg as a maintenance treatment after L1 in aggressive G1/2 DP-NET should be confirmed.
TRIAL REGISTRATION
NCT02288377 (clinicaltrials.gov).

Identifiants

pubmed: 36087395
pii: S0959-8049(22)00480-4
doi: 10.1016/j.ejca.2022.07.033
pii:
doi:

Substances chimiques

Peptides, Cyclic 0
lanreotide 0G3DE8943Y
Somatostatin 51110-01-1

Banques de données

ClinicalTrials.gov
['NCT02288377']

Types de publication

Clinical Trial, Phase II Journal Article Randomized Controlled Trial Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

31-40

Informations de copyright

Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.

Déclaration de conflit d'intérêts

Conflict of interest statement Côme Lepage worked as a member of the advisory board for Novartis, personal fees from Novartis, IPSEN, grants from Merck, IPSEN. Thomas Walter worked as a member of advisory boards for AAA, IPSEN, Keocyt and Novartis. Astrid Lièvre reports grants from Bayer Lilly, Merck and Novartis; personal fees from AAA, Amgen, Bayer, Bristol-Myers Squibb, Celgene, HalioDx, Incyte, Ipsen, Lilly, Merck, Novartis, Pierre Fabre, Roche, Sandoz, Sanofi and Servier; non-financial support from AAA, Amgen, Bayer, Incyte, Ipsen, Merck, Novartis, Pierre Fabre, Pfizer, Roche, Sandoz, Servier and Integragen. David Tougeron reports grants from Bristol-Myers Squibb and Novartis; personal fees from Amgen, Bayer, Bristol-Myers SquibbIpsen, Novartis, Pierre Fabre, Roche, Sanofi and Servier. Catherine Lombard-Bohas worked as a member of advisory boards for AAA, IPSEN, Keocyt, Novartis. Jean-Louis Legoux worked as a member of an advisory board for Novartis, reports personal fees from Novartis, Pfizer (clinical research), Novartis, Keocyt, Servier (courses, training), Merck, Servier, Keocyt (invitations to national or international congresses). All remaining authors have no conflicts of interest to declare.

Auteurs

Côme Lepage (C)

EPICAD INSERM UMR LNC 1231, University of Burgundy Franche Comté, Dijon, France; Department of HGE & Digestive Oncology, University Hospital Dijon, University of Burgundy, Dijon, France. Electronic address: come.lepage@u-bourgogne.fr.

Jean-Marc Phelip (JM)

Department of HGE & Digestive Oncology, University Hospital St Etienne, France.

Astrid Lievre (A)

Department of Gastroenterology, Rennes University Hospital, Rennes 1 University, INSERM U1242 "Chemistry Oncogenesis Stress Signalling", Rennes, FFCD, France.

Karine Le-Malicot (K)

EPICAD INSERM UMR LNC 1231, University of Burgundy Franche Comté, Dijon, France.

Laetitia Dahan (L)

C.H.U. la Timone and Université de la Méditerranée, Marseille, France.

David Tougeron (D)

Department of Hepato-gastroenterology, Poitiers University Hospital and Poitiers University, Poitiers, France.

Christos Toumpanakis (C)

Centre for Gastroenterology, Neuroendocrine Tumour Unit, ENETS Centre of Excellence, Royal Free Hospital, London, UK.

Frédéric Di-Fiore (F)

Normandie University, UNIROUEN, Inserm 1245, IRON Group, Hôpital Universitaire de Rouen, Centre Henri-Becquerel, Département d'oncolgie Médicale, Service d'hépato-gastroentérologie, 76000 Rouen, France.

Catherine Lombard-Bohas (C)

Cancer Institute, ENETS Centre of Excellence, Hospices Civils de Lyon, France.

Ivan Borbath (I)

Department of Gastroenterology, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium.

Romain Coriat (R)

AP-HP, Université Paris Descartes, Faculté de Médecine, Hôpital Cochin, Gastroenterology and Endoscopy Unit, Sorbonne Paris Cité, 75014 Paris, France.

Thierry Lecomte (T)

Department of HGE & Digestive Oncology, University Hospital Tours, François-Rabelais University, Tours, France.

Rosine Guimbaud (R)

Centre Hospitalier Universitaire de Toulouse, Toulouse, France.

Caroline Petorin (C)

Digestive Surgery and Oncological Department, Hospital Estaing, Clermont-Ferrand, France.

Jean-Louis Legoux (JL)

Department of Hepato-Gastroenterology, La Source Hospital, Orléans, France.

Pierre Michel (P)

Normandie University, UNIROUEN, Inserm 1245, IRON Group, Hôpital Universitaire de Rouen, Centre Henri-Becquerel, Département d'oncolgie Médicale, Service d'hépato-gastroentérologie, 76000 Rouen, France.

Jean-Yves Scoazec (JY)

Department of Pathology, University Paris-Saclay, Gustave Roussy Cancer Center, Villejuif, France.

Denis Smith (D)

Hôpital Haut Lévêque, Service d'hépato-gastroentérologie, Pessac, France.

Thomas Walter (T)

Cancer Institute, ENETS Centre of Excellence, Hospices Civils de Lyon, France.

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