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Published on: October 27, 2014
Efficacy of Anti-VEGF Drugs Based Combination Therapies in Recurrent Glioblastoma: Systematic Review and
Vinod Solipuram1, Ramin Soltani2, B P Venkatesulu3,4
1Department of Medicine, Saint Agnes Hospital, Baltimore, MD, USA.
Background:
Recurrent glioblastoma multiforme (rGBM) has a grim prognosis, with current therapies offering no survival benefit. Several combination therapies involving anti-VEGF agents have been studied with mixed results.
Methods:
A systematic search was performed using five electronic databases: PubMed, Scopus, ISI, Embase, and the Cochrane Library, without language limitations. The primary outcome of interest was progression-free survival (PFS). Secondary outcomes were overall survival (OS), objective response ratio (ORR), and grade ≥ 3 adverse events. Estimates for PFS and OS were calculated as random effects hazard ratio (HR) with 95% confidence intervals (CIs) using the generic inverse variance method. Estimates for ORR and grade ≥ 3 adverse events were calculated using a random-effects risk ratio (RR) with 95% confidence intervals (CIs) using the Mantel-Haenszel method.
Results:
Thirteen studies met the inclusion criteria and a total of 1994 patients were included in the analysis. There was no statistically significant improvement in PFS (HR 0.84; 95% CI (0.68, 1.03); I2=81%), OS (HR 0.99; 95% CI (0.88, 1.12); I2=0%), and ORR (RR 1.36; 95% CI (0.96, 1.92); I2=61%) in the combination therapy group when compared to the control group. Significantly higher grade ≥ 3 adverse events (RR 1.30; 95% CI (1.14, 1.48); I2=47%) were seen in the combination therapy when compared to the control group.
Conclusion:
Our analysis showed that the use of combination therapy with anti-VEGF agents did not offer any benefit in PFS, OS, or ORR. In contrast, it had significantly higher grade 3-5 adverse events. Further studies are needed to identify effective therapies in rGBM that can improve survival.
Insights
Combination therapy with anti-VEGF agents does not improve survival outcomes for recurrent glioblastoma multiforme (rGBM). This approach also leads to a significant increase in severe adverse events, indicating a need for alternative treatments.
Area of Science:
- Neuro-oncology
- Clinical trial analysis
- Pharmacological research
Background:
- Recurrent glioblastoma multiforme (rGBM) presents a significant clinical challenge with limited therapeutic options.
- Current treatments for rGBM offer no demonstrable survival benefit.
- Anti-VEGF agents have been investigated in combination therapies for rGBM with varied outcomes.
Purpose of the Study:
- To systematically evaluate the efficacy and safety of combination therapies involving anti-VEGF agents in patients with recurrent glioblastoma multiforme.
- To determine the impact of these combination therapies on progression-free survival (PFS), overall survival (OS), and objective response ratio (ORR).
- To assess the incidence of severe adverse events associated with these treatment regimens.
Main Methods:
- A systematic literature search was conducted across five major electronic databases (PubMed, Scopus, ISI, Embase, Cochrane Library).
- Inclusion criteria were applied to thirteen studies involving 1994 patients.
- Primary outcome was PFS; secondary outcomes included OS, ORR, and grade ≥ 3 adverse events, analyzed using random-effects models.
Main Results:
- Combination therapy with anti-VEGF agents did not yield statistically significant improvements in PFS (HR 0.84; 95% CI (0.68, 1.03)) or OS (HR 0.99; 95% CI (0.88, 1.12)).
- Objective response ratio (ORR) also showed no significant benefit (RR 1.36; 95% CI (0.96, 1.92)).
- A significant increase in grade ≥ 3 adverse events was observed in the combination therapy group (RR 1.30; 95% CI (1.14, 1.48)).
Conclusions:
- Combination therapy using anti-VEGF agents is not effective in improving survival or response rates for recurrent glioblastoma multiforme.
- These combination therapies are associated with a higher incidence of severe adverse events.
- Further research is essential to discover and validate novel therapeutic strategies for rGBM that can enhance patient survival.
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