![Sample our Medicine, Dentistry, Nursing & Allied Health journals, sign in here to start your FREE access for 14 days]({"type":"image" , "src" : "/sda/5944/TOC-Subject-Sample-2021-Medicine-Dentistry-Nursing-Allied-Health.jpg"})
ABSTRACT
Introduction
The paucity of the therapeutic armamentarium currently available for patients with malignant mesothelioma clearly represents a huge unmet need. Over the last years, based on new advances in understanding the biology of mesothelioma, new therapeutic approaches have been investigated.
Areas covered
In this manuscript, the literature data regarding the advances in drug treatment for patients with mesothelioma are critically reviewed, focusing particularly on immunotherapy and targeted therapy.
Expert opinion
The latest findings on immunotherapy and targeted therapy are changing the therapeutic armamentarium for mesothelioma. However, mesothelioma comprises genomically different subtypes and the phenotypic diversity combined with the rarity of this disease represents a major criticality in developing new effective therapies. Although the first clinical data are encouraging, the treatment’s stratification by molecular characteristics for mesothelioma is only at the beginning. Luckily, the rapid improvement of understanding the biology of mesothelioma is producing new opportunities in discovering new therapeutic targets to test in pre-clinical settings and to transfer in the clinical setting. In this evolving scenario, the future perspectives for mesothelioma patients seem really promising.
Article highlights box
The paucity of the therapeutic armamentarium currently available for MM patients represents clearly a huge unmet need.
Thank to new advances in the knowledge of the MM biology, an increasing interest has been reserved to new therapeutic strategies, such as immunotherapy and targeted therapies.
The immunotherapy revolution is implementing mesothelioma’s therapeutic armamentarium.
There is a robust rationale supporting angiogenesis inhibition in mesothelioma. Two randomized trials showed a survival advantage of bevacizumab combined with cisplatin plus pembrolizumab and ramucirumab combined with gemcitabine.
The low disease prevalence, the difficulties in patient recruitment, and the interpatient genomic heterogeneity in mesothelioma are driving the emergence of stratified therapy, highlighting the necessity of predictive biomarkers helping patient selection.
In order to achieve a higher receptivity and flexibility in the approval standards for orphan drugs regarding the evidence base, closer collaboration with the regulatory authorities is mandatory.
In this evolving scenario, the future perspectives for mesothelioma patients seem really promising.
Abbreviations
| AEs | = | adverse events |
| BSC | = | Best Supportive Care |
| CR | = | complete response |
| CTLA-4 | = | cytotoxic T lymphocyte antigen 4 |
| DC | = | dendritic cell |
| DCR | = | disease control rate |
| EMA | = | European Medicines Agency |
| FAP | = | fibroblast activation protein |
| FDA | = | Food and Drug Administration |
| FGFR | = | fibroblast growth factor receptors |
| FLT3 | = | Fms Related Receptor Tyrosine Kinase 3 |
| ICIs | = | immune checkpoint inhibitors |
| ITT | = | intention-to-treat |
| MiST | = | Mesothelioma Stratified Therapy |
| MM | = | malignant mesothelioma |
| mOS | = | median overall survival |
| mPFS | = | median progression-free survival |
| MPM | = | malignant pleural mesothelioma |
| NK | = | natural killer |
| ORR | = | overall response rate |
| OS | = | overall survival |
| PD-1 | = | programmed death-1 |
| PDGFR | = | platelet-derived growth factor receptor |
| PD-L1 | = | programmed death ligand-1 |
| PFS | = | progression-free survival |
| PR | = | partial response |
| RET | = | REarranged during Transfection |
| RR | = | response rate |
| SD | = | stability of disease |
| TAAs | = | tumor-associated antigens |
| TILs | = | Tumor-infiltrating limphocytes |
| TKIs | = | Tyrosine kinase inhibitors |
| Treg | = | regulatory T |
| UPenn | = | University of Pennsylvania |
| VEGF | = | vascular endothelial growth factor |
| VEGFR | = | vascular endothelial growth factor receptor |
| WT-1 | = | Wilms tumour-1 |
Declaration of interest
P Zucali reports outside the submitted work personal fees for an advisory role, speaker engagements and travel and accommodation expenses from Merck Sharp & Dohme (MSD), Astellas, Janssen Pharmaceuticals, Sanofi, Ipsen, Pfizer, Novartis, Bristol-Myers Squibb, Amgen, AstraZeneca, Roche, and Bayer. A Santoro reports outside the submitted work personal fees for serving as a consultant and/or advisor for Arqule, Sanofi, Bristol-Myers Squibb, Servier, Gilead Sciences, Pfizer, Eisai, Bayer and Merck Sharp & Dohme (MSD). 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
In the past three years, one reviewer has received consulting fees from Ikena, Takeda, GlaxoSmithKline (2020), Aldeyra Therapeutics, Novocure, and honoraria for CME content from PER, Medscape, Research to Practice, Medical Learning Institute and OncLive. The same reviewer’s research institution receives research funding from the Department of Defense, the National Institutes of Health, Precog, GlaxoSmithKline, Epizyme, Polaris, Sellas Life Sciences, Bristol-Myers Squibb, Millenium/Takeda, Curis, and Atara for research conducted by the reviewer. The same reviewer also serves on the board of directors of the Mesothelioma Applied Research Foundation, uncompensated. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.