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. 2022 Sep:172:357-366.
doi: 10.1016/j.ejca.2022.06.020. Epub 2022 Jul 11.

Lurbinectedin shows clinical activity and immune-modulatory functions in patients with pre-treated small cell lung cancer and malignant pleural mesothelioma

Daphne W Dumoulin  1 , Luca Cantini  2 , Robin Cornelissen  1 , Madelief Vink  1 , Larissa Klaase  1 , Kick Slooff  1 , Nura Tebayna  1 , Joanne M Mankor  1 , Sara J Baart  3 , Rudi Hendriks  1 , Anne-Marie C Dingemans  1 , Marcella Willemsen  1 , Joachim G J V Aerts  4
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Free article

Lurbinectedin shows clinical activity and immune-modulatory functions in patients with pre-treated small cell lung cancer and malignant pleural mesothelioma

Daphne W Dumoulin et al. Eur J Cancer. 2022 Sep.
Free article

Abstract

Purpose: Lurbinectedin is a promising new drug being investigated in pre-treated patients with small cell lung cancer (SCLC) or malignant pleural mesothelioma (MPM). Its clinical activity in the real-world setting has not been investigated yet.

Patients and methods: Clinical data of patients with SCLC and MPM who were treated with lurbinectedin were prospectively collected. Comprehensive immune cell profiling by flow cytometry was performed on screening and treating peripheral blood samples.

Results: A total of 95 patients (43 SCLC and 52 MPM) were treated, mostly as ≥3-line of therapy. In the SCLC cohort, a median progression-free survival (mPFS) was 1.5 months (95% CI: 1.4-3.0), and median overall survival was 7.0 months (95% CI: 4.7-not reached). Objective radiological response and disease control rate after 12 weeks were 16% and 28%, respectively. In the MPM cohort, median progression-free survival was 2.8 months (95% CI: 1.4-4.2), and median overall survival was 7.2 months (95% CI: 5.9-not reached). Disease control rate after 12 weeks was 29%, whereas no partial responses were registered. No new safety signals were observed. Lurbinectedin treatment was significantly associated with the depletion of circulating classical monocytes, which correlated with a better PFS in patients with SCLC. Lurbinectedin increased the proliferation of CD4+ and CD8+ T cells (SCLC) and natural killer and natural killer T cells (SCLC and MPM) and altered co-stimulatory and co-inhibitory receptor expression on circulating lymphocytes.

Conclusion: Lurbinectedin has a manageable safety profile and shows clinical activity in pre-treated patients with SCLC and MPM. Its immune-modulatory functions make lurbinectedin a potential platform for immunotherapy combinations.

Keywords: Lurbinectedin; immune monitoring; immunotherapy; malignant pleural mesothelioma/MPM; small cell lung cancer/SCLC.

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Conflict of interest statement

Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The authors declare no relevant conflict of interest related to the published manuscript. Relevant financial activities outside the submitted work: DD reports receiving speakers fee from BMS, Roche, Pfizer, and Novartis. LC is granted by ESMO with an ESMO Translational Research Fellowship. Any views, opinions, findings, conclusions, or recommendations expressed in this material are those solely of the author(s) and do not necessarily reflect those of ESMO. RC reports consulting for Roche, MSD, Boehringer Ingelheim and receiving speaker's fee from BMS, Roche, Pfizer, Boehringer Ingelheim, Novartis. AD reports receiving grants from Bristol-Myers Squibb, AbbVie, and Amgen; and other fees from Roche, Eli Lilly, Boehringer Ingelheim, AstraZeneca, Bristol-Myers Squibb, Amgen, Novartis, Merck Sharp & Dohme, Takeda, and PharmaMar outside of the submitted work. JGJVA reports receiving commercial research grants from Amphera, Eli-Lilly and Roche, holds ownership interest (including patents) in Amphera BV, and is a consultant/advisory board member for Amphera, Boehringer Ingelheim, Bristol-Myers Squibb, Eli-Lilly, MSD, Takeda, Bayer, Astra Zeneca and Roche. The other authors have no conflicts of interest to declare.

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