Lurbinectedin as second- or third-line palliative therapy in malignant pleural mesothelioma: an international, multi-centre, single-arm, phase II trial (SAKK 17/16).


Journal

Annals of oncology : official journal of the European Society for Medical Oncology
ISSN: 1569-8041
Titre abrégé: Ann Oncol
Pays: England
ID NLM: 9007735

Informations de publication

Date de publication:
04 2020
Historique:
received: 29 10 2019
revised: 20 12 2019
accepted: 24 12 2019
pubmed: 23 2 2020
medline: 7 1 2021
entrez: 23 2 2020
Statut: ppublish

Résumé

Systemic second- and third-line therapies for malignant pleural mesothelioma (MPM) result in a median progression-free survival (mPFS) of <2 months and median overall survival (mOS) of 6-9 months. Lurbinectedin binds to the DNA of the regulatory region while inhibiting tumour-associated macrophage transcription. In early trials, encouraging outcomes occurred in patients (pts) with MPM treated with lurbinectedin. We aimed to generate lurbinectedin efficacy and safety data among pts with progressive MPM. Pts with progressing MPM treated with first-line platinum-pemetrexed chemotherapy with or without immunotherapy received lurbinectedin monotherapy. Treatment was given intravenously at 3.2 mg/m Forty-two pts from nine centres across Switzerland and Italy were recruited. Histology was epithelioid in 33 cases, sarcomatoid in 5, and biphasic in 4. Overall 10/42 (23.8%) underwent prior immunotherapy and 14/42 (33.3%) had progressed ≤6 months after first-line chemotherapy. At data cut-off PFS The primary efficacy endpoint was reached with acceptable toxicity. Lurbinectedin showed promising activity regardless of histology, prior immunotherapy, or outcome on prior treatment. CLINICALTRIALS. NCT03213301.

Sections du résumé

BACKGROUND
Systemic second- and third-line therapies for malignant pleural mesothelioma (MPM) result in a median progression-free survival (mPFS) of <2 months and median overall survival (mOS) of 6-9 months. Lurbinectedin binds to the DNA of the regulatory region while inhibiting tumour-associated macrophage transcription. In early trials, encouraging outcomes occurred in patients (pts) with MPM treated with lurbinectedin. We aimed to generate lurbinectedin efficacy and safety data among pts with progressive MPM.
PATIENTS AND METHODS
Pts with progressing MPM treated with first-line platinum-pemetrexed chemotherapy with or without immunotherapy received lurbinectedin monotherapy. Treatment was given intravenously at 3.2 mg/m
RESULTS
Forty-two pts from nine centres across Switzerland and Italy were recruited. Histology was epithelioid in 33 cases, sarcomatoid in 5, and biphasic in 4. Overall 10/42 (23.8%) underwent prior immunotherapy and 14/42 (33.3%) had progressed ≤6 months after first-line chemotherapy. At data cut-off PFS
CONCLUSIONS
The primary efficacy endpoint was reached with acceptable toxicity. Lurbinectedin showed promising activity regardless of histology, prior immunotherapy, or outcome on prior treatment. CLINICALTRIALS.
GOV IDENTIFIER
NCT03213301.

Identifiants

pubmed: 32085891
pii: S0923-7534(20)35926-3
doi: 10.1016/j.annonc.2019.12.009
pii:
doi:

Substances chimiques

Carbolines 0
Heterocyclic Compounds, 4 or More Rings 0
PM 01183 0

Banques de données

ClinicalTrials.gov
['NCT03213301']

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

495-500

Informations de copyright

Copyright © 2020 European Society for Medical Oncology. Published by Elsevier Ltd. All rights reserved.

Déclaration de conflit d'intérêts

Disclosure YM declares travel grants as well as advisory fees from PharmaMar paid to his institution. RvM declares advisory fees from PharmaMar paid to his institution. All other authors have declared no conflicts of interest.

Auteurs

Y Metaxas (Y)

Department of Oncology/Haematology, Kantonsspital Graubünden, Chur, Switzerland. Electronic address: ioannis.metaxas@ksgr.ch.

M Früh (M)

Department of Medical Oncology and Haematology, Kantonsspital St. Gallen, St Gallen, Switzerland; University of Bern, Bern, Switzerland.

E I Eboulet (EI)

SAKK Coordinating Centre, Bern, Switzerland.

F Grosso (F)

Mesothelioma Unit - Oncology, SS. Antonio and C. Arrigo Hospital, Alessandria, Italy.

M Pless (M)

Department of Medical Oncology and Haematology, Kantonsspital Winterthur, Winterthur, Switzerland.

P A Zucali (PA)

Humanitas Cancer Centre, Humanitas Research Hospital, Rozzano, Italy.

G L Ceresoli (GL)

Oncology Unit, Humanitas Clinic Gavazzeni, Bergamo, Italy.

M Mark (M)

Department of Oncology/Haematology, Kantonsspital Graubünden, Chur, Switzerland.

M Schneider (M)

SAKK Coordinating Centre, Bern, Switzerland.

A Maconi (A)

Scientific Research and Development Department, SS Antonio e Biagio e Cesare Arrigo, General Hospital, Alessandria, Italy.

M Perrino (M)

Humanitas Cancer Centre, Humanitas Research Hospital, Rozzano, Italy.

C Biaggi-Rudolf (C)

SAKK Coordinating Centre, Bern, Switzerland.

P Froesch (P)

Department of Oncology, Ospedale Regionale di Bellinzona e Valli, Bellinzona, Switzerland.

S Schmid (S)

Department of Medical Oncology and Haematology, Kantonsspital St. Gallen, St Gallen, Switzerland.

C Waibel (C)

Division of Haematology and Oncology, Kantonsspital Baden, Baden, Switzerland.

C Appenzeller (C)

Department of Medical Oncology and Haematology, Kantonsspital St. Gallen, St Gallen, Switzerland.

D Rauch (D)

Oncology Centre, Hospital STS AG, Thun, Switzerland.

R von Moos (R)

Department of Oncology/Haematology, Kantonsspital Graubünden, Chur, Switzerland.

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Classifications MeSH