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Effectiveness and Safety of Trabectedin or Lurbinectedin for refractory Malignant Pleural Mesothelioma: A Systematic Review and Meta-Analysis


Advanced malignant pleural mesothelioma (MPM) is generally treated with platinum/pemetrexed-based first-line therapy. There are few treatment options following disease progression. Recent studies of lurbinectedin and trabectedin in patients with MPM demonstrated promising results. Therefore, we performed a systematic review and meta-analysis to assess the effectiveness and safety of both Lurbinectedin and Trabectedin for treating MPM following progression with first-line treatment options.


The objective of this study is to evaluate the effectiveness and safety of Lurbinectedin and Trabectedin as treatment options for advanced malignant pleural mesothelioma (MPM) in patients who have experienced disease progression after receiving platinum/pemetrexed-based first-line therapy


We searched PubMed, the Cochrane Library, and Embase databases to identify published studies on second and third-line treatments for recurrent or advanced mesothelioma. Inclusion criteria were as follows: (1) studies with 20 or more patients; (2) studies assessing the outcomes of interest; and (3) studies published in English. The main outcome of interest was PFS. Heterogeneity was assessed with the Cochran Q test and I2 statistics. Random effects models were used for all statistical analyses, which were performed using R software (v.4.2.2).


Three studies were included (2 non-randomized clinical trials and a prospective cohort), with a total of 240 patients. In a pooled analysis, progression-free survival (PFS) after 12 weeks was 38%, (95% CI 0.28-0.49) and mean progression-free survival was 2 months (95% CI 2 to 4 months). The most common adverse events (AEs) were neutropenia, fatigue, and hepatotoxicity. The proportion of neutropenia was 25% (95% CI 0.13-0.36).


Lurbinectedin and trabectedin has a manageable safety profile and shows clinical activity in pre-treated patients with MPM. While the observed PFS rates and adverse events underscore the potential benefits and challenges associated with these therapies, further research endeavors are warranted to better elucidate their long-term efficacy, comparative effectiveness, and potential integration into clinical practice.


Lurbinectedin, Trabectedin, malignant pleural mesothelioma, third-line

Financiador do resumo


Estudo Clínico - Tumores de Pulmão e Tórax


MARIA INEZ DACOREGIO, Rafaela de Almeida Cardoso Góes, Isabella Ferreira Michelon, Davi Said Gonçalves Celso, José Henrique Agner Ribeiro, Maysa Vilbert