Emerging treatments
Pembrolizumab
Pembrolizumab, an anti-programmed cell death protein 1 (PD-1) monoclonal antibody, modestly improved objective response compared with single-agent chemotherapy in an open-label randomised phase 3 trial of patients with relapsed malignant pleural mesothelioma.[91] In a subsequent open-label phase 3 trial, adding pembrolizumab to cisplatin (or carboplatin) plus pemetrexed improved survival compared with chemotherapy alone in untreated patients with advanced pleural mesothelioma.[92]
TEA domain (TEAD) transcription factor inhibitors
The Hippo pathway represents a novel treatment pathway for various cancers.[93][94] TEAD inhibitors (e.g., IK-930) have demonstrated potential utility in the treatment of unresectable NF2-deficient malignant pleural mesothelioma, with a phase 1 trial currently in progress.[95][96] IK-930 has received fast track designation from the US Food and Drug Administration (FDA) to treat unresectable NF2-deficient mesothelioma.
Anti-antigen therapies
Immunotherapies targeting antigens that are differentially overexpressed in mesothelioma compared with normal tissue is another area of active investigation. Transcription factor, WT1, and tumour differentiation antigen, mesothelin, are particularly promising in this regard. Mesothelin-targeted interventions that are in clinical trials include an antibody, antibody drug conjugates, vaccine, immunotoxins, and chimeric antigen receptor (CAR) T cells.
Intrapleural chemotherapy
Intrapleural therapy would seem a promising method to deliver anti-neoplastic agents because they potentially treat the entire at-risk area of the hemithorax and lung. Intrapleural interventions that are under investigation include chemotherapies, photodynamic therapy, anti-mesothelin CAR T cells, oncolytic measles viruses, and gene therapy with tumour selective adenoviruses.
Cannabis‐based medicines
One Cochrane review in early 2023 identified no clear benefit from tetrahydrocannabinol (THC) and/or cannabidiol (CBD) for the treatment of moderate‐to‐severe opioid‐refractory cancer pain, including when compared to opioids or consultant palliative care.[97]
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Clinicians may consider therapeutic trials on an individual basis. The review also acknowledged the need for further research, giving multiple recommendations.
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