Long-term benefit of lurbinectedin as palliative chemotherapy in progressive malignant pleural mesothelioma (MPM): final efficacy and translational data of the SAKK 17/16 study.

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Version: Final published version
License: CC BY-NC-ND 4.0
Serval ID
serval:BIB_FA0FF9C4B3E9
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Long-term benefit of lurbinectedin as palliative chemotherapy in progressive malignant pleural mesothelioma (MPM): final efficacy and translational data of the SAKK 17/16 study.
Journal
ESMO open
Author(s)
Mark M., Rusakiewicz S., Früh M., Hayoz S., Grosso F., Pless M., Zucali P., Ceresoli G.L., Maconi A., Schneider M., Froesch P., Tarussio D., Benedetti F., Dagher J., Kandalaft L., von Moos R., Tissot-Renaud S., Schmid S., Metaxas Y.
ISSN
2059-7029 (Electronic)
ISSN-L
2059-7029
Publication state
Published
Issued date
12/04/2022
Peer-reviewed
Oui
Volume
7
Number
3
Pages
100446
Language
english
Notes
Publication types: Journal Article
Publication Status: aheadofprint
Abstract
The SAKK 17/16 study showed promising efficacy data with lurbinectedin as second- or third-line palliative therapy in malignant pleural mesothelioma. Here, we evaluated long-term outcome and analyzed the impact of lurbinectedin monotherapy on the tumor microenvironment at the cellular and molecular level to predict outcomes.
Forty-two patients were treated with lurbinectedin in this single-arm study. Twenty-nine samples were available at baseline, and seven additional matched samples at day one of cycle two of treatment. Survival curves and rates between groups were compared using the log-rank test and Kaplan-Meier method. Statistical significance was set at P value <0.05.
Updated median overall survival (OS) was slightly increased to 11.5 months [95% confidence interval (CI) 8.8-13.8 months]. Thirty-six patients (85%) had died. The OS rate at 12 and 18 months was 47% (95% CI 32.1% to 61.6%) and 31% (95% CI 17.8% to 45.0%), respectively. Median progression-free survival was 4.1 months (95% CI 2.6-5.5 months). No new safety signals were observed. Patients with lower frequencies of regulatory T cells, as well as lower tumor-associated macrophages (TAMs) at baseline, had a better OS. Comparing matched biopsies, a decrease of M2 macrophages was observed in five out of seven patients after exposure to lurbinectedin, and two out of four patients showed increased CD8+ T-cell infiltrates in tumor.
Lurbinectedin continues to be active in patients with progressing malignant pleural mesothelioma. According to our very small sample size, we hypothesize that baseline TAMs and regulatory T cells are associated with survival. Lurbinectedin seems to inhibit conversion of TAMs to M2 phenotype in humans.
Keywords
M2 phenotype, lurbinectedin, malignant pleural mesothelioma, regulatory T cells, tumor-associated macrophages, tumor-infiltrating lymphocytes
Pubmed
Open Access
Yes
Create date
25/04/2022 11:40
Last modification date
14/07/2022 6:37
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