Abstract
Malignant pleural mesothelioma (MPM) is a rare malignancy characterized by very poor prognosis and lack of treatment options. Immunotherapy has rapidly emerged as an effective tool for MPM, particularly for tumors of non-epithelioid histology. At the same time, comprehensive genomic sequencing may open the way to new-generation targeted-drugs able to hit specific MPM molecular vulnerabilities. These innovations will possibly enrich, but also dramatically complicate, the elucidation of treatment algorithms. Multidisciplinary integration is urgently needed.
Highlights
Malignant pleural mesothelioma (MPM) is a deadly malignancy arising from mesothelial cells of the pleural surface, accounting for fewer than 1% of all cancers [1,2,3]
In a retrospective analysis conducted by Patil and colleagues [17], a sample of 99 MPM specimens were profiled for immune gene expression and PD-L1 expression, proposing a classification in three subgroups according to the degree of inflamed phenotype: 60% of the samples analyzed showed an inflamed status, making mesothelioma a good theoretical candidate to immunotherapy
In the pivotal phase III trial Checkmate 743, ipilimumab and nivolumab led to a significantly 4-month median OS (mOS) improvement in a first-line setting compared to platinum-based doublet chemotherapy (18.1 vs. 14.1 months; HR 0.74 96.6% CI: 0.60–0.91; p = 0.0020)
Summary
Malignant pleural mesothelioma (MPM) is a deadly malignancy arising from mesothelial cells of the pleural surface, accounting for fewer than 1% of all cancers [1,2,3]. The epithelioid histology is associated with a more favorable prognosis and occurs in 60–80% of patients, whereas the sarcomatoid histology (20% of cases) has worse outcomes, with a lower chance of response to therapy [7]. Multimodality therapy including induction platinum-based chemotherapy, surgical resection (pleurectomy/decortication with mediastinal lymph node sampling or extrapleural pneumonectomy), and sometimes radiation therapy is generally offered to young patients with good performance status, localized disease, and epithelioid histological subtype [8,9]. Pemetrexed-based re-treatment should be considered for patients who have obtained a PFS greater than 3 months with first-line therapy [12,13], while other active drugs, such as gemcitabine and vinorelbine, can be used for platinum-refractory patients with a good PS [14,15,16]. We critically review these new emerging options of treatment for MPM, moving from the actual therapeutic strategies to upcoming practice-change future approaches
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