A Comparison Between Chemo-Radiotherapy Combined With Immunotherapy and Chemo-Radiotherapy Alone for the Treatment of Newly Diagnosed Glioblastoma: A Systematic Review and Meta-Analysis

Abstract

BackgroundImmunotherapy for GBM is an emerging field which is increasingly being investigated in combination with standard of care treatment options with variable reported success rates.ObjectiveTo perform a systematic review of the available data to evaluate the safety and efficacy of combining immunotherapy with standard of care chemo-radiotherapy following surgical resection for the treatment of newly diagnosed GBM.MethodsA literature search was performed for published clinical trials evaluating immunotherapy for GBM from January 1, 2000, to October 1, 2020, in PubMed and Cochrane using PICOS/PRISMA/MOOSE guidelines. Only clinical trials with two arms (combined therapy vs. control therapy) were included. Outcomes were then pooled using weighted random effects model for meta-analysis and compared using the Wald-type test. Primary outcomes included 1-year overall survival (OS) and progression-free survival (PFS), secondary outcomes included severe adverse events (SAE) grade 3 or higher.ResultsNine randomized phase II and/or III clinical trials were included in the analysis, totaling 1,239 patients. The meta-analysis revealed no statistically significant differences in group’s 1-year OS [80.6% (95% CI: 68.6%–90.2%) vs. 72.6% (95% CI: 65.7%–78.9%), p = 0.15] or in 1-year PFS [37% (95% CI: 26.4%–48.2%) vs. 30.4% (95% CI: 25.4%–35.6%) p = 0.17] when the immunotherapy in combination with the standard of care group (combined therapy) was compared to the standard of care group alone (control). Severe adverse events grade 3 to 5 were more common in the immunotherapy and standard of care group than in the standard of care group (47.3%, 95% CI: 20.8–74.6%, vs 43.8%, 95% CI: 8.7–83.1, p = 0.81), but this effect also failed to reach statistical significance.ConclusionOur results suggests that immunotherapy can be safely combined with standard of care chemo-radiotherapy without significant increase in grade 3 to 5 SAE; however, there is no statistically significant increase in overall survival or progression free survival with the combination therapy.

The need for paradigm shift: prognostic significance and implications of standard therapy-related systemic immunosuppression in glioblastoma for immunotherapy and oncolytic virotherapy

“…A few studies have argued that immunosuppression does not prevent immune responses induced by a vaccine in patients with glioblastoma ( 189 ) and have pointed to a putative positive immunomodulatory role of temozolomide in dendritic cell vaccination or multimodal immunotherapy ( 190 , 191 ). However, no large, well-designed randomized controlled trials have been conducted to prove the positive effects of the addition of immunotherapy or oncolytic virotherapy to standard therapy, and only minor subsets of patients have benefited from conducted clinical trials ( 3 – 7 ).…”

“…Clinical trials of immunotherapies, including vaccines and oncolytic viruses, have demonstrated encouraging efficacy in minor subsets of patients with progressive/recurrent glioblastoma (3)(4)(5)(6)(7)(8). Different patient selection criteria, recombinant viruses, protocols for vaccine preparation, and schedules and routes of vaccine or virus administration have been applied in trials.…”

The IAP antagonist birinapant enhances chimeric antigen receptor T cell therapy for glioblastoma by overcoming antigen heterogeneity

“… 3 , 4 GBM is the most common and aggressive brain cancer, and it remains incurable with a median survival time of 16.9 months under the current standard of care. 5 CAR T cell therapies targeting GBM have shown evidence of anti-tumor activity in early-phase studies. 6 , 7 , 8 However, there remain numerous challenges.…”

Glioblastoma Multiforme Selective Nanomedicines for Improved Anti-Cancer Treatments

“…After diagnosis, currently accepted treatments include surgical tumour resection followed by radiotherapy and concomitant chemotherapy with temozolomide (TMZ) [ 7 , 8 ]. Unfortunately, studies show that even with this combined approach, fewer than 25% of patients survive more than two years [ 9 , 10 ]. The major limitations of these treatments lie in the significant side effects of the chemotherapeutics and the inability of those drugs to selectively eliminate residual GBM cells, which often leads to recurrences.…”