A systematic review of immunotherapies in combination with temozolomide as treatment for glioblastoma

Glioblastomas comprise a significant percentage of malignant adult central nervous system tumor cases and patients typically do not survive longer than a year after diagnosis. There are few treatment options for patients which meaningfully prolong survival other than chemotherapy, radiotherapy, and surgery. There are many clinical trials examining immunotherapy-chemotherapy combination treatments. This systematic review uses database research of clinical trials to identify randomized controlled immunotherapy-temozolomide combination trials which evaluate the median overall and progression-free survival in adult patients. The review also assesses the study design of selected trials for risk of bias. The desired outcomes are presented as they are reported in the selected studies and are evaluated based on reported statistical significance. We included 10 studies in the final selection and found five studies focused on bevacizumab as an immunotherapy in combination with temozolomide while five used unique interventions. Of those studies, only bevacizumab and autologous dendritic cell vaccination reported an improvement in desired outcomes compared to the control. The risk of bias analysis identified only one study with high risk of bias and five studies with unclear risk of bias in blinding. Our study identifies promising treatments and recommends further examination of those interventions but does not make any recommendations on changes to current glioblastoma treatments. The authors have no funding or conflict of interests to declare. The authors followed the Preferred Reporting Items for Systematic reviews and MetaAnalyses guidelines for writing this review.