Lurbinectedin in patients with pretreated neuroendocrine tumours: Results from a phase II basket study.
Lurbinectedin
Neuroendocrine tumours
Phase II trial
Small cell
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:
Sep 2022
Sep 2022
Historique:
received:
24
01
2022
revised:
03
06
2022
accepted:
10
06
2022
pubmed:
14
7
2022
medline:
17
8
2022
entrez:
13
7
2022
Statut:
ppublish
Résumé
Patients with neuroendocrine tumours (NETs) need alternative therapies after failure of first-line therapy. This phase II trial evaluated lurbinectedin, a selective inhibitor of oncogenic transcription, at 3.2 mg/m Two of 31 evaluable patients had confirmed partial responses (ORR = 6.5%; 95%CI, 0.8-21.4%). Median DoR was 4.7 months (95% CI, 4.0-5.4 months), median PFS was 1.4 months (95% CI, 1.2-3.0 months) and median OS was 7.4 months (95% CI, 3.4-16.2 months). Lurbinectedin showed an acceptable, predictable and manageable safety profile. The most common grade 3/4 toxicity was neutropenia (40.6%; grade 4, 12.4%; febrile neutropenia, 3.1%). Considering the exploratory aim of this trial that evaluated a heterogeneous population of NETs patients, and the signs of antitumour activity observed (two confirmed partial responses and seven long disease stabilisations), further development of lurbinectedin is warranted in a more selected NETs population. Sponsor Study Code: PM1183-B-005-14. EudraCT number: 2014-003773-42. gov reference: NCT02454972.
Sections du résumé
BACKGROUND
Patients with neuroendocrine tumours (NETs) need alternative therapies after failure of first-line therapy.
PATIENTS AND METHODS
This phase II trial evaluated lurbinectedin, a selective inhibitor of oncogenic transcription, at 3.2 mg/m
RESULTS
Two of 31 evaluable patients had confirmed partial responses (ORR = 6.5%; 95%CI, 0.8-21.4%). Median DoR was 4.7 months (95% CI, 4.0-5.4 months), median PFS was 1.4 months (95% CI, 1.2-3.0 months) and median OS was 7.4 months (95% CI, 3.4-16.2 months). Lurbinectedin showed an acceptable, predictable and manageable safety profile. The most common grade 3/4 toxicity was neutropenia (40.6%; grade 4, 12.4%; febrile neutropenia, 3.1%).
CONCLUSIONS
Considering the exploratory aim of this trial that evaluated a heterogeneous population of NETs patients, and the signs of antitumour activity observed (two confirmed partial responses and seven long disease stabilisations), further development of lurbinectedin is warranted in a more selected NETs population.
TRIAL REGISTRATION NUMBER
Sponsor Study Code: PM1183-B-005-14. EudraCT number: 2014-003773-42.
CLINICALTRIALS
gov reference: NCT02454972.
Identifiants
pubmed: 35830841
pii: S0959-8049(22)00375-6
doi: 10.1016/j.ejca.2022.06.024
pii:
doi:
Substances chimiques
Carbolines
0
Heterocyclic Compounds, 4 or More Rings
0
PM 01183
0
Banques de données
ClinicalTrials.gov
['NCT02454972']
Types de publication
Clinical Trial, Phase II
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
340-348Informations de copyright
Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.
Déclaration de conflit d'intérêts
Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Cristian Fernández, Carmen Kahatt, Vicente Alfaro, Mariano Siguero and Ali Zeaiter are permanent employees of PharmaMar. Victor Moreno reports consulting fees from Roche, Bayer, BMS, Janssen and Basilea. Vivek Subbiah reports grants from Pharmamar, Eli Lilly/LOXO Oncology, Blueprint Medicines Corporation, Turning Point Therapeutics, Boston Pharmaceuticals; and grants from Helsinn Pharmaceuticals during the conduct of the study; in addition, Vivek Subbiah reports a grant and advisory board/consultant position with Eli Lilly/Loxo Oncology during the conduct of the study; research grants from Roche/Genentech, Bayer, GlaxoSmithKline, Nanocarrier, Vegenics, Celgene, Northwest Biotherapeutics, Berghealth, Incyte, Fujifilm, D3, Pfizer, Multivir, Amgen, Abbvie, Alfa-sigma, Agensys, Boston Biomedical, Idera Pharma, Inhibrx, Exelixis, Blueprint Medicines, Altum, Dragonfly Therapeutics, Takeda, National Comprehensive Cancer Network, NCI-CTEP, University of Texas MD Anderson Cancer Center, Turning Point Therapeutics, Boston Pharmaceuticals, Novartis, Pharmamar, Medimmune; an advisory board/consultant position with Helsinn, Incyte, QED Pharma, Daiichi-Sankyo, Signant Health, Novartis, Janssen, Relay Therapeutics, Roche, Medimmune; travel funds from Pharmamar, Incyte, ASCO, ESMO; other support from Medscape; all outside the submitted work. No disclosures were reported by the other authors.