The Role of Checkpoint Inhibitors in Glioblastoma

AbstractGiven its poor prognosis, glioblastoma represents an area of high unmet clinical need. Standard of care for the treatment of glioblastoma in the frontline setting is limited to surgical resection, radiation, and temozolomide, with the more recent addition of Tumor Treating Fields. Several agents, including bevacizumab, lomustine, and carmustine have been approved in the recurrent setting. To date, no therapies have demonstrated substantial survival benefit beyond standard of care. An expanding understanding of the role of the immune system in fighting cancer has led to the development and approval of various immunotherapeutic approaches across solid tumors. In glioblastoma, the notion of a highly immune-restricted central nervous system has also evolved, further providing the  rationale for testing therapies that promote immune trafficking to the CNS and infiltration into the tumor to counteract the immunosuppressive mechanisms that support tumor progression. There are five broad categories of immunotherapies currently being tested in GBM: vaccines, cytokine therapy, on colytic viral therapy, chimeric antigen receptor T cell therapy, and checkpoint inhibitors. This review focuses on checkpoint inhibitors in GBM, the rationale for its use, preclinical data, and early clinical experience. Efficacy data are limited, and while a number of late-stage trials are ongoing, early trials showed no benefit in survival. There is a dizzying array of combinations being tested in c...

Source: Targeted Oncology - July 8, 2019 Category: Cancer & Oncology Source Type: research