10204-CS-21 Exploratory analyses from the INDIGO study on the mechanism of seizure control by vorasidenib through tumor volume reduction
Bibliographic record
Abstract
Abstract Background Patients with grade 2 IDH1/2 mutant (mIDH1/2) gliomas may experience symptoms (e. g. seizures) that impact their daily lives. Vorasidenib, an oral, brain-penetrant, dual inhibitor of mIDH1/2, has shown significant clinical benefits, including gradual tumor shrinkage, and a manageable safety profile in the Phase 3 INDIGO study. Herein, we investigate the potential relationship between vorasidenib and seizure rate, and between tumor volume and seizure activity in patients with mIDH1/2 glioma. Methods Patients aged >12 years with grade 2 mIDH1/2 oligodendroglioma or astrocytoma, no prior treatment for glioma other than surgery, and no uncontrolled seizures were randomized 1:1 to receive vorasidenib 40 mg or placebo daily. Exploratory analyses for the number of on-treatment seizures were conducted in patients with more than 1 seizure in the baseline or on-treatment periods using a negative binomial regression model. The potential association between seizure activity and tumor volume was assessed using the mixed-effect model with repeated measurements. P-values were not prespecified. Results This analysis included 168 patients treated with vorasidenib (oligodendroglioma: n = 88; astrocytoma: n = 80) and 163 patients treated with placebo (oligodendroglioma: n = 84; astrocytoma: n = 79). Patients treated with vorasidenib had lower on-treatment rates of seizures than those treated with placebo (model-estimated rate of on-treatment seizures per person-year: 18.2 [95% confidence interval (CI) 8.4, 39.5] vs 51.2 [95% CI 22.9, 114.8]; ratio of rates: 0. 36 [95% CI 0.14, 0. 89]; P = 0.0263). There was a highly positive correlation between tumor volume and seizure number (log tumor size estimate of coefficient: 0.7; standard error: 0.26; P = 0.007). Conclusion Treatment with vorasidenib was associated with lower seizure activity than with placebo in patients with mIDH1/2 glioma. Smaller tumor volume was associated with a lower seizure rate. Since treatment with vorasidenib also leads to gradual tumor shrinkage, these results suggest a potential mechanism of seizure control by tumor size reduction with vorasidenib.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".