Targeted research is advancing the treatment of pleural mesothelioma. Results from a study on a novel protein inhibitor known as tazemetostat (brand name Tazverik) were recently released. It is showing impressive results as a second line treatment for mesothelioma patients with the BAP1 genetic mutation. The control rate for disease was 54.1 percent at 12 weeks and 32.8 percent at 24 weeks. These results exceeded expectations which is great news because there are not enough second line treatments available for pleural mesothelioma. Mesothelioma is a notoriously hard to treat cancer, so any new treatment is welcome.
Tazemetostat is an EZH2 blocker, an enzyme that inhibits the genes that suppress cancer tumor growth. The trial looked at patients that expressed the BAP1 gene, which causes a higher expression of EZH2, leading to accelerated cancer growth. This treatment is not meant for everyone, instead it is a precise and focused medication. The BAP1 mutation is found in over half of patients with mesothelioma. Targeted therapy is a new concept for mesothelioma treatment, so BAP1 is just one gene that could be targeted for mesothelioma. In the future, mesothelioma could be categorized into more groups that could benefit from specific targeted treatments.
Tazemetostat is currently approved for treating synovial sarcoma, non-Hodgkin lymphoma, and certain solid tumors. The clinical trial was performed in the United States, United Kingdom, and France. The United States locations include City of Hope Cancer Treatment and Research Center in Duarte, California; Mayo Clinic in Rochester, Minnesota; UCLA Comprehensive Cancer Center in Los Angeles; University of California-San Francisco Medical Center; Dana Farber Cancer Institute in Boston; Memorial Sloan Kettering Cancer Center in New York City; and Massachusetts General Hospital in Boston.
There were 70 patients in the study with the BAP1 gene mutation. The patients had been previously treated and the cancer either returned or stopped responding to the treatment. After patients started the tazemetostat treatment regimen, which was given in 21-day cycles, progression free survival was improved to 12 weeks and the median overall survival was improved to 41 weeks. There were less than five percent of patients who had serious side effects.
The 54.1 percent disease control rate after 12 weeks could either be a complete response, partial response, or stable disease. The stable disease rate was 62 percent. Epizyme, the company that created the treatment, is promoting it as a second line treatment for multiple cancers previously treated with chemotherapy. Other studies are also looking at targeting the BAP1 genetic mutation. Currently a phase II trial is looking at a different protein inhibitor called niraparib on multiple cancers including mesothelioma. Talozaparib, a similar drug to niraparib and tazemetostat, is being tested on mesothelioma patients with the BAP1 mutation. Another study being done by the National Cancer Institute is looking at BAP1 and how presence of the mutation can predispose people to mesothelioma and detection of the mutation can lead to early detection of the disease.
The best treatment currently for mesothelioma is a combination of surgery, chemotherapy, and radiation. The problem is that only around one third of patients diagnosed with mesothelioma can receive surgery. Tazemetostat is one treatment that could potentially improve mesothelioma treatment by treating patients whose cancer stopped responding to treatment. Tazemetostat is the first targeted therapy that has been shown to be effective for mesothelioma. Now that more mesothelioma alterations are being discovered, more targeted therapies could be created to specifically treat these alterations.
