One of this year’s American Society for Clinical Oncology (ASCO) updates in mesothelioma included the release of the first results for the Phase 2 Study of the EZH2 inhibitor, tazemetostat, for malignant mesothelioma, presented by the chair of the board of the Mesothelioma Applied Research Foundation (Meso Foundation), Marjorie Zauderer, MD.
This study enrolled 61 BAP1 loss-of-function mesothelioma patients who had been previously treated with at least two other lines of therapy, and who had relapsed or never had a response.
“We are always searching for promising new treatments for patients with mesothelioma, particularly for those with relapsed or refractory disease,” said Dr. Zauderer, medical oncologist and co-director of the Mesothelioma Program at Memorial Sloan Kettering Cancer Center. “These findings show that tazemetostat monotherapy substantially delayed disease progression without significant toxicities, which is clinically meaningful. This is encouraging for the patients and families impacted by mesothelioma, and for the oncologists who treat them.”
In particular, the primary endpoint of the study, defined as disease control, exceeded expectations with 51% of patients reaching a complete response, partial response, or stable disease (versus the anticipated minimum of 35%) at 12 weeks. At 24 weeks, 26% of patients maintained disease control.
The therapy was administered orally twice daily. Although five patients had dose reductions based on side-effects, no patients quit the study. Side-effects were manageable and included fatigue, decreased appetite, dyspnea, nausea, and cancer pain.
This therapy targets mesothelioma by inhibiting EZH2, an enzyme that, when BAP1 protein is absent, suppresses genes that inhibit tumor growth. Therefore, the idea is that by keeping EZH2 in check with tazemetostat, important tumor suppressor genes previously turned off by the presence of EZH2, become turned on and able to serve a protective purpose against cancer. One such gene in particular, which is familiar to mesothelioma patients, is the BAP1 gene. When the gene loses its ability to suppress cancer, the process is called a BAP1 loss-of-function.
