Analysis Of The Efficacy And Safety Of Immune Checkpoint Inhibitor PD-1 Antibody Therapy In Glioblastoma Multiforme

BackgroundGlioblastoma(WHO grade Ⅳ glioma,GBM)is the most common malignant brain tumor,that has aggressive biological behavior and resistance to treatment.Over the years,progress has been made in maximally possible surgical resection,radiation therapy,and chemotherapeutic strategies,yet the current patients’median overall survival is around 14.6 months,and the median progression-free survival time is only 6.9 months.Researchers continue to explore new treatments for glioblastoma.In recent years,immune checkpoint inhibitor therapy has achieved good efficacy in many tumors,but the efficacy and safety of immune checkpoint inhibitor therapy for glioblastoma remains to be explored.MethodChapter One:A comprehensive electronic literature search of Embase,Web of Science,Cochrane Library and PubMed was conducted.The main evaluation data were the OS rate at 12 months and the PFS rate at 6 months.The secondary evaluation data was the incidence of serious adverse events(grade 3 or greater AEs).The study was performed using R "meta" package.Chapter two:Survival analysis of newly diagnosed glioblastoma patients treated with PD-1 immune checkpoint inhibitors,and newly diagnosed glioblastoma patients treated with the standard Stupp regimen at the Department of Radiotherapy,Southern Hospital of Southern Medical University.The relevant baseline data were collected for the included population,and were followed up regularly to obtain survival data such as overall survival time and progression-free survival time,as well as the incidence of immunotherapy-related adverse effects.ResultChapter One:A total of 7 research studies met the inclusion criteria,comprising a total of 343 patients with recurrent glioblastoma enrolled in 10 study cohorts.Among patients receiving immunotherapy(without regard to adjuvant as well as neoadjuvant immunotherapy),12 months overall survival fluctuated between 19%and 69.0%,with an overall 12 months survival rate of 40%,and among the adjuvant immunotherapy cohort,12 months overall survival with anti-PD-1/PD-Ll adjuvant immunotherapy fluctuated between 19%and 58%,with an overall after meta-analysis survival rate was 38%.The 12-months overall survival rate for neoadjuvant PD-1/PD-L1 immune checkpoint inhibitors fluctuated between 60%and 69%,with an overall survival rate of 65%at 12 months after meta-analysis.The 6month progression-free survival rate for the recurrent glioblastoma cohort(without differentiation between adjuvant and neoadjuvant immunotherapy)fluctuated between 0 and 40%,with a progression-free survival rate of 16.0%at 6 months after meta-analysis.Progression-free survival at 6 months fluctuated between 0%and 35%in the cohort treated with adjuvant PD-1/PD-L1 immune checkpoint inhibitors for relapsed glioblastoma,with a progression-free survival rate of 13%at 6 months after meta-analysis.Progression-free survival at 6 months for patients with relapsed glioblastoma treated with neoadjuvant PD-1/PD-L1 immune checkpoint inhibitors ranged from 31%to 40%,with a progression-free survival rate of 35%at 6 months after meta-analysis.Compared to bevacizumab-targeted therapy and chemotherapy,there was no statistically significant difference in progression-free survival at 6 months,although significantly improved 12-month survival in recurrent glioblastoma.And the overall incidence of immunotherapy toxicity was lower compared to targeted therapy.Chapter two:A total of 53 patients with glioblastoma met the inclusion criteria in our center,of which 13 patients were included in the immunotherapy combined with the Stupp regimen treatment group and 40 patients were included in the standard Stupp regimen treatment group.The Kaplan-Meier survival analysis concluded that the introduction of immune checkpoint inhibitors into the first-line treatment of patients with newly diagnosed glioblastoma significantly improved the patients is median survival and had acceptable toxicity.ConclusionImmune checkpoint inhibitors in combination with the Stupp regimen for patients with newly diagnosed glioblastoma can further improve patient survival compared to the Stupp regimen.The toxicity of adding immunotherapy to the Stupp regimen is acceptable.This still requires further randomized controlled clinical trials to assess the specific efficacy as well as the safety of immune checkpoint inhibitor therapy in combination with the Stupp regimen in all age groups with primary glioblastoma.