ABSTRACT
Introduction: Malignant pleural mesothelioma (MPM) has limited treatment options with minimal new therapy approvals for unresectable disease in the past 15 years. However, considerable work has occurred to develop immunotherapies and biomarker driven therapy to improve patient outcomes over this period.
Areas covered: This review examines current standard of care systemic therapy in the first- and second line setting. The last 12 months has seen 2 significant trials (Checkmate 743 and CONFIRM) which provide evidence supporting the role of immunotherapy in the management of MPM. Further trials are underway to assess the role of combination chemoimmunotherapy and personalized therapy. Additionally, a large number of clinical trials are ongoing to assess the efficacy of oncoviral, dendritic cell, anti-mesothelin and chimeric antigen receptor T cell therapy in the treatment of MPM.
Expert opinion: Recent Phase III trial results have established a role for immunotherapy in the management of MPM. The optimal sequencing and combination of chemotherapy and immunotherapy remains to be determined. Novel therapies for MPM are promising however efficacy remains to be determined and issues remain regarding access to and delivery of these therapies.
List of Abbreviations
BAP1 – BRCA associated protein 1
BRCA – Breast cancer associated gene
BSC – Best Supportive Care
CAR-T – Chimeric Antigen Receptor T cells
CDK – Cyclin dependent kinase
CLS - Capillary leak syndrome
CTLA4 - Cytotoxic T-lymphocyte-associated protein 4
DC – Dendritic cells
EGFR – Epidermal Growth Factor Receptor
EPP - Extra-pleural pneumonectomy
FDA - Food & Drug Administration
ICI – Immune Checkpoint Inhibitors
miRNA – Micro ribonucleic acid
MPM – Malignant pleural mesothelioma
MSLN – Mesothelin
NSCLC – Non small cell lung cancer
OS – Overall Survival
PARP - Poly(adenosine diphosphate-ribose) polymerase
PD-L1 - Programmed Death Ligand 1
PFS – Progression Free Survival
rAd - Replication deficient adenoviruses
TAAs – Tumor Associated Antigens
TTFields – Tumor Treating Fields
USA – United States of America
VEGF - Vascular Endothelial Growth Factor
Declaration of interest
N Pavlakis sits on advisory boards for Boehinger, MSD, Merck, BMS, Astra Zeneca, Takeda, Pfizer, Roche & Ipsen. NP has speaking honoraria with Boehringer, Bayer, Novartis, Pfizer, Roche, Takeda & Ipsen. NP research institution receives funding from Bayer, Pfizer and Roche. S Kao receives honoraria from Astra Zeneca, Roche, Boehinger, Pfizer, BMS, MSD & Takeda. Astra Zeneca provides research funding to SKs institution. SK has received reimbursement for travel & accommodation from BMS, Roche & Boehringer. M Boyer has disclosures from Amgen, BMS, MSD, Pfizer, Genentech/Roche, Astra Zeneca, Novartis, Immugene, Earli & Eli Lilly. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
Reviewer disclosures
Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.