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Shervin Taslimi et al.
of the University of Toronto in Canada compared the efficacy of phase 2 and phase 3 clinical randomized controlled trials using different treatment regimens for relapsed GBM, and conducted a network meta-analysis to provide a basis
for the treatment of relapsed GBM.
Article published online
in the February 2021 issue of Neurooncol Adv.
—Excerpted from the article chapter
【Ref: Taslimi S, et al.
Neurooncol Adv.
2021 Feb 12; 3(1).
doi: 10.
1093/noajnl/vdab029.
】
Research background
The prognosis of glioblastoma (GBM) is extremely poor, with a two-year survival rate of less than 30%; And there is a problem
of recurrence.
Shervin Taslimi of the University of Toronto et al.
compared the efficacy of phase 2 and phase 3 clinical randomized controlled trials (RCTs) on relapsed GBM with different treatment regimens, and conducted a network meta-analysis to provide a basis
for the treatment of relapsed GBM.
Article published online
in the February 2021 issue of Neurooncol Adv.
Research methods
in each group, according to the Priority Reporting Entry (PRISMA) guidelines of systematic reviews and meta-analyses.
The primary endpoint outcome of the study was overall survival (OS) in patients with relapsed GBM, and the secondary endpoint outcome measures were progression-free survival (PFS) and side effects
.
The Cochrane Risk of bias risk assessment tool was used to assess the quality of
RCTs.
Because VEGF inhibitors may have an effect on MRI-T2 FLAIR signaling, the authors performed sensitivity analyses
for PFS.
Research results
A total of 2194 patients with relapsed GBM from 15 studies were included in the meta-analysis at low
risk of bias.
The incidence of MGMT promoter methylation was 16.
9% and IDH mutation was 2.
7%
for the entire study cohort.
Anti-VEGF drugs are the most common drugs in trials, and other common treatments include anti-TGF-β, nitrosourea alkylating agents, and anti-PD-1; There were 1383 patients in the treatment group and 811 patients in
the control group.
A total of 1784 patients in eight studies had complete survival data, 387 received a single anti-VEGF treatment, and 729 received a combination of anti-VEGF and another drug
.
Among them, anti-VEGF drugs, including bevacizumab, cederanib, and regorafenib
.
The combination of TTF and anti-VEGF had the greatest effect on OS compared with lomustine alone (HR = 0.
51; 95% CI, 0.
15 to 0.
73); The combination of TTF and anti-VEGF may be the optimal treatment for relapsed GBM (P = 0.
803).
PFS data were complete for 1264 patients from seven studies, 372 received a single anti-VEGF treatment, and 618 received a combination of anti-VEGF and another drug
.
The combination of anti-VEGF and lomustine was better than lomustine alone in prolonging PFS (HR = 0.
57; 95% CI, 0.
41-0.
79).
The combination of anti-VEGF and gefitinib was slightly better than lomustine in improving PFS (HR = 0.
63; 95% CI, 0.
28 to 1.
38).
Simultaneous use of anti-VEGF and lomustine may be the optimal regimen to prolong PFS (P = 0.
86), followed by anti-VEGF plus gefitinib (P = 0.
72); The sensitivity analysis was consistent
with the above conclusions.
Meta-analysis
was not performed due to high heterogeneity between studies reporting side effects.
In general, there are more adverse effects
with multiple treatments.
Cedilinib / gefitinib had the highest frequency of grade 3 or 4 adverse events, with an average of 2.
53 episodes per person
.
The TTF was 1.
32 times/person, and the overall incidence of grade 5 adverse reactions was extremely low
.
Conclusion of the study
Finally, the authors note that a network meta-analysis of RCT data on relapsed GBM found that combination therapy may be more effective
than monotherapy.
Although the field of exploration is broad, due to the high heterogeneity of relapsed GBM, it is difficult to draw strong conclusions between groups and to obtain a consensus
on effective treatment of relapsed GBM.
Further studies are recommended to clarify specific treatment options and to conduct subgroup analyses
.
