Adding levetiracetam to standard of care led to better survival overall, but certain patient subgroups may derive a greater benefit, according to a preprint study that has not yet been peer-reviewed.
Key Takeaways
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A meta-analysis found that adding levetiracetam to standard of care in patients with glioblastoma led to better overall survival.
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The authors caution, however, that this combination may not be effective for all patients.
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Some subgroups may benefit more from add-on levetiracetam — specifically, patients with lower rates of MGMT methylation and female patients.
Why This Matters
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Prognosis in glioblastoma is poor, with a median overall survival of about 15 months.
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New treatments are needed to improve outcomes.
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Levetiracetam is an antiepileptic drug that might improve the efficacy of temozolomide chemotherapy, but results from past investigations have been mixed.
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In the absence of data from randomized trials, a pooled analysis of previous studies provides the best clinical insight.
Study Design
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Investigators searched PubMed and other databases up to May 2021 to identify relevant studies.
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Hazard ratios, median overall survival, and adverse events were pooled using random-effect models.
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The 20 selected studies included 5804 patients with glioblastoma treated with standard-of-care therapy, 1923 (33%) of whom also received levetiracetam.
Key Results
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Of the 11 studies included in the survival analysis, the authors observed improved overall survival in patients who received levetiracetam, though the results were not significant (HR, .89; P = .094).
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However, looking at six studies that provided median overall survival and confidence interval data, the authors found pooled median overall survival was significantly longer in patients receiving levetiracetam vs those who did not (6.2 months longer; P < .01).
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On meta-regression, levetiracetam treatment effect decreased with greater rates of MGMT methylation (P = .02) and increased with greater proportions of female patients (P = .002).
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Levetiracetam add-on therapy did not increase the odds of adverse events.
Limitations
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The studies were most often of “fair” or “good” quality, but many patients were lost to follow-up or were not followed for an appropriate duration.
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There was significant heterogeneity across the studies, including in how methylation status was determined.
Disclosures
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No outside funding or author conflicts of interest were reported.
This summary of preprint research study, “The Effect of Levetiracetam Treatment on Survival in Patients with Glioblastoma: A Systematic Review and Meta-Analysis,” has not been peer reviewed. The full text can be found at researchsquare.com.
M. Alexander Otto is a physician assistant with a master’s degree in medical science, and an award-winning medical journalist who has worked for several major news outlets before joining Medscape. He is an MIT Knight Science Journalism fellow. Email: [email protected].
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