[Systemic Treatment of Malignant Pleural Mesothelioma]

Malignant pleural mesothelioma(MPM)is a highly aggressive tumor with a poor prognosis and an increasing incidence worldwide. The only standard first-line chemotherapy for patients with unresectable MPM is cisplatin(CDDP)plus peme- trexed(PEM)(CDDP/PEM), with a median overall survival of about 12months and a median progression-free survival(PFS) of less than 6 months. There are no treatments with proven benefit on survival for relapsed MPM patients. Therefore, novel therapeutic strategies are urgently required. Several molecular pathways involved in MPM have been identified; these include growth factor signaling pathways, cell cycle regulation, apoptosis, and angiogenesis. Fortunately, several agents targeting these processes have yielded promising results in preliminary trials. The addition of vascular endothelial growth factor(VEGF) inhibitor bevacizumab to the standard CDDP/PEM provides a 2.7-month survival benefit. Triple angiokinase inhibitor nintedanib, inhibiting the VEGFR, PDGFR, and FGFR, plus standard chemotherapy demonstrated a significant improvement in median PFS of 3.7 months in the overall study population, and a greater median PFS benefit of 4.0 months in epithelioid MPM. Mesothelin is an attractive target protein expressed on mesothelioma cells. Amatuximab, a chimeric anti-mesothelin antibody, in combination with CDDP/PEM, is currently being tested in randomized, double-blind, placebo-controlled phase II study. Anetumab ravtansine, mesothelin-directed antibody drug conjugate, was evaluated in a randomized trial to compare to vinorelbine in patients with MPM who have high mesothelin expression and have progressed on CDDP/PEM-based first-line chemotherapy. However, anetumab ravtansine was not superior to vinorelbine in primary endpoint of PFS(4.3 months vs 4.5 months). Immune checkpoint blockades have demonstrated promising preclinical and clinical results in several cancer types, and are currently being investigated in clinical trials for MPM patients. PD-L1 expression in tumor tissue of MPM was reported, ranging between 20% and 70%. PD-L1 expression was significantly associated with a worse survival and overexpression was more common in sarcomatoid histology. This review summarizes clinical results for the latest systemic treatments in MPM.