Nobukazu Fujimoto

By Nobukazu Fujimoto

Targeting immunocheckpoint with immunomodulatory monoclonal antibodies has proven to be an effective antitumor strategy across a variety of cancers. The immunosuppressive tumor microenvironment in malignant pleural mesothelioma (MPM) has suggested that MPM might benefit from this kind of immunotherapy. In recent years, immunocheckpoint inhibitors (ICIs) have shown encouraging results for patients with MPM. Antibodies against programmed death 1 (PD-1) and PD-ligand 1 (PD-L1) have demonstrated favorable response, progression-free survival, and overall survival. The toxicity profiles were similar to those observed with ICIs in other malignancies, like melanoma and non-small cell lung cancer, and they appeared to be manageable. Nivolumab, an anti-PD-1 antibody, was approved in Japan for advanced or metastatic MPM patients resistant or intolerant to other chemotherapies. Important future issues include developing a combination therapy, where ICIs are combined with other agents (including other ICIs), and developing biomarkers for determining which patients might respond well and which might experience unacceptable toxicities.

Part of the book: Asbestos-related Diseases

By Asako Matsuda and Nobukazu Fujimoto

Malignant pleural mesothelioma (MPM) is an extremely aggressive plural malignancy mainly caused by asbestos exposure. Basic research about the immune suppressive tumor microenvironment in MPM has suggested that MPM might be a good candidate for immune therapy. Immunocheckpoint inhibitors have shown some promising results. A phase Ib trial with pembrolizumab, an antibody specific for the programmed cell death 1 protein (anti-PD-1), showed efficacy in patients with programmed death-ligand 1 (PD-L1)-positive MPM. Among 25 patients tested, 5 patients (20%) achieved a partial response. A Japanese group evaluated the efficacy and safety of nivolumab, an anti-PD-L1 antibody, for patients with advanced MPM in a phase II study. Ten (29%) patients showed an objective response. Based on those results, nivolumab was approved in Japan for unresectable recurrent MPM. A phase III randomized study was conducted to compare nivolumab plus ipilimumab to platinum doublet chemotherapy as a first-line therapy in unresectable MPM. The primary endpoint, overall survival (OS), was significantly improved in the nivolumab plus ipilimumab group. Cellular therapies and cancer vaccines are limited by many challenges; therefore, improvements to overcome these difficulties are urgently warranted. Further research is needed, including large-scale clinical trials, to clarify the utility and safety of immunotherapy in MPM.

Part of the book: Advances in Precision Medicine Oncology

By Fumie Onishi and Nobukazu Fujimoto

Malignant pleural mesothelioma (MPM) is a neoplasm strongly associated with past exposure to asbestos. In general, the prognosis of patients with MPM is poor; however, in recent years, some encouraging results have been reported for systemic therapies for MPM. In a randomized phase III study, the combination of nivolumab and ipilimumab improved overall survival, compared to the standard platinum-based chemotherapy. An important clinical issue is whether the outcome of patients with MPM might be further improved by combining immunotherapies with cytotoxic chemotherapy and/or angiogenesis inhibitors. This chapter covers recent findings on systemic therapies, including cytotoxic chemotherapy, anti-angiogenic inhibitors, and/or immune checkpoint inhibitors.

Part of the book: Mesothelioma