When it comes to treating mesothelioma, little has changed in that regard over many years until the last couple years and even more recently. Before 2020, the only treatment that was shown to improve overall survival in patients with malignant pleural mesothelioma was chemotherapy in combination with platinum and anti-folate, and no systemic therapy had been shown to improve overall survival of patients in the second line setting until that same year.
In clinical trials, systemic therapy is the only treatment that has been shown to increase overall survival in mesothelioma patients.
Surgery
There are two main options when it comes to surgery: an extrapleural pneumonectomy (EPP), which involves the resection of the lung with the visceral pleura, what is left of the parietal pleura and the ipsilateral hemidiaphragm, or an extended pleurectomy/decortication (eP/D), which involves an extrapleural dissection to take out the tumor. Macroscopic complete resection surgery is usually used as a tri-modality therapy along with other treatments. The goal of an extended pleurectomy/decortication is a macroscopic complete resection surgery. eP/D has been shown to be more effective than EPP.
Radiation
Radiation therapy is usually used either peri operatively or palliatively. Neoadjuvant radiation was studied in the Surgery for Mesothelioma After Radiation Therapy clinical trial. This was a phase 2, single arm study. All patients involved in the study who began treatment also completed EPP.
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Chemotherapy
Until recently, chemotherapy was the only form of mesothelioma treatment to increase overall survival in patients. A phase 3 clinical trial was done by Vogelzang et al and it showed a benefit in median overall survival for patients who received a combination of pemetrexed and cisplatin chemotherapy. This study caused the FDA to approve the combination of pemetrexed and cisplatin as the first line treatment for those with malignant pleural mesothelioma.
Tumor Treating Fields
At first, malignant pleural mesothelioma is a localized disease, so it affects a certain area of the body before it spreads to distant areas. Researchers want to discover treatments that can be directed to the pleural cavity in a safe way. Tumor Treating Fields are for solid tumors and they deliver low intensity electric fields to the site of the tumor. There is evidence from a phase 3 trial in glioblastoma multiforme showing that adding TTFields to chemotherapy can improve overall survival.
The phase 2 study, STELLAR, was a single arm trial looking at the activity of TTFields combined with pemetrexed and platinum chemotherapy. There were 80 patients who participated in the study and the median overall survival was 18.2 months.
Immune Checkpoint Inhibitors
Those who research mesothelioma and try to find new advancements in treatment have a growing interest in the roles of immune checkpoint inhibitors. Immune checkpoint inhibitors can be used to act against the Programmed cell death protein 1 (PD-1), Programmed Death Ligand 1 (PD-L1) or Cytotoxic T-Lymphocyte-associated protein 4 (CTLA4) to cause an antitumor immune response. This has been observed in a multitude of single arm studies. Studies that observed the effects of immune checkpoint inhibitors on mesothelioma patients in the second line setting were the CONFIRM and PROMISE-Meso trials.
Targeted Therapy
There have been tries to come up with targeted therapy options for the treatment of mesothelioma. When a patient has mesothelioma, their genes are altered. BAP1 is the most altered gene in patients, with 57 percent of patients being BAP1 deficient. Also, 38 percent of patients may be BRCA deficient. There have been studies done to assess the efficacy of targeting these cells.
Overall, the advances of mesothelioma treatment and the new directions that treatment is going in could be beneficial for mesothelioma patients now and in the future.
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