New Hope for Relapsed Pleural Mesothelioma?

There is new evidence that adding a drug called vorinostat to immunotherapy might help relapsed pleural mesothelioma patients. 

The new study comes from the Moffitt Cancer Center in Tampa. It focused on patients with non-small cell lung cancer. Non-small cell lung cancer is similar to pleural mesothelioma in many ways. 

The study found that patients who received vorinostat along with an immune checkpoint inhibitor had better results. The findings could be good news for relapsed pleural mesothelioma patients, too.

Different Immunotherapy Drugs

Vorinostat is sold under the brand name Zolinza. It is a histone deacetylase (HDAC) inhibitor. HDAC inhibitors alter the way proteins are expressed inside cells. They also stimulate the immune system. 

Immune checkpoint inhibitors (ICIs) like Keytruda also stimulate the immune system. ICIs block proteins like PD-1 that help mesothelioma cells evade detection. Drugs like Keytruda are among the most promising new mesothelioma treatment approaches. 

Relapsed pleural mesothelioma can happen when patients become resistant to their ICI. The new study shows vorinostat helped Keytruda work again in mice with relapsed lung cancer. 

“HDAC inhibitors improve response to PD-1 blockade in mouse models of lung cancer by increasing T-cell trafficking to tumors and enhancing T-cell function,” says Amer Beg, PhD, an immunologist at Moffitt.

Second-Line Treatment Needed for Relapsed Pleural Mesothelioma

Right now, there is no second-line treatment for relapsed pleural mesothelioma. A 2011 study of vorinostat for mesothelioma produced disappointing results. That study tested vorinostat as a stand-alone treatment.

The Moffitt study is the first one to combine vorinostat with an ICI in lung cancer. After the encouraging results in mice, researchers tested the combination in 33 human lung cancer patients. 

The treatment caused fatigue, nause, and vomiting in about a third of patients. But 67 percent of them experienced at least a partial response. Tumors stopped growing in 16 patients. Patients who had higher levels of T cells before treatment had the best results. 

The results of the Moffiitt study suggest that vorinostat may boost the effectiveness of Keytruda for relapsed pleural mesothelioma. 

The next step is a phase 2 trial of vorinostat and Keytruda as a first-line lung cancer treatment. 

Source:

“New Drug Combination Shows Promising Activity in Non-Small Cell Lung Cancer Patients”, August 27, 2019, Moffit Cancer Center website, https://moffitt.org/newsroom/press-release-archive/2019/new-drug-combination-shows-promising-activity-in-non-small-cell-lung-cancer-patients/

Gray, J, et al, “Phase 1/1b study of pembrolizumab plus vorinostat in advanced/metastatic non-small cell lung cancer”, August 24, 2019, Clinical Cancer Research, https://clincancerres.aacrjournals.org/content/early/2019/08/13/1078-0432.CCR-19-1305