Malignant pleural mesothelioma (MPM) is a cancer with high mortality rate and few therapeutic options. Its incidence is growing fast worldwide and is associated with asbestos exposure, a well known cancerogenic factor driving the development of this cancer. Generally MPM is diagnosed at an advanced inoperable stage and most frequently the only therapeutic approach is palliative chemotherapy. Platinum-pemetrexed doublets prolong significantly median overall survival (OS) and median progression free survival (PFS) with respect to platinum alone and are considered the only therapeutic option in a first line setting. Unfortunately, essentially all patients usually progress and die subsequently to a first line therapyl. There is strong evidence that the immune system is deeply involved in the biogenesis of MPM and that an imbalance in pro-inflammatory cytokines and exhausted adaptive T-cell mediated immune response are the main causes of neoangiogenesis, progression and metastatisation processes. Newer immunotherapeutic agents act on regulatory molecules expressed on immune cells in order to increase T cell activity and immune response against tumor. The anti-cytotoxic T lymphocyte antigen 4 (anti-CTLA4) demonstrated activity and a long-term disease control (DC) rate in advanced pretreated MPM in phase II study even if these results are not confirmed in more recently Phase IIb randomized trial versus placebo (DETERMINE study). Antibodies against Programmed Death 1 receptor (PD-1) and its ligand (PD-L1) are highly promising new agents regulating immune check-point processes. In particular the interaction of these agents takes place peripherally more than in the lymphoid tissue and may explain the higher response rate and lower adverse immune effects in comparison to antiCTLA4 agents. AntiPD-L1 antibodies are widely studied in many Phase I-II trials in different advanced pretreated solid tumors independent of tumor PD-L1 expression, with promising results and long-term survival. Ongoing melanoma and lung cancer phase III trials would probably better define the role of this class of drugs in clinical practice. Durvalumab is a human IgG1 antibody which binds specifically to PD-L1, preventing binding to PD-1 and CD80. Numerous Phase II-III clinical trials are underway evaluating Durvalumab either as monotherapy or combination with evidence of activity in a wide range of solid tumors. Durvalumab has received FDA approval as second line treatment in patients with locally advanced or metastatic urothelial carcinoma.~Given these prospects for PD-L1 Ab, a Phase II study is proposed in order to evaluate the activity and safety of Durvalumab in advanced pretreated MPM.
Malignant pleural mesothelioma (MPM) is a cancer with high mortality rate and few therapeutic options.essentially all patients usually progress and die subsequently to a first line therapyl. There is strong evidence that the immune system is deeply involved in the biogenesis of MPM and that an imbalance in pro-inflammatory cytokines and exhausted adaptive T-cell mediated immune response are the main causes of neoangiogenesis, progression and metastatisation processes.Numerous Phase II-III clinical trials are underway evaluating Durvalumab either as monotherapy or combination with evidence of activity in a wide range of solid tumors. Durvalumab has received FDA approval as second line treatment in patients with locally advanced or metastatic urothelial carcinoma.~Given these prospects for PD-L1 Ab, a Phase II study is proposed in order to evaluate the activity and safety of Durvalumab in advanced pretreated MPM.