PDCT-07. HERBY (BO25041): A PHASE II OPEN-LABEL, RANDOMIZED, MULTICENTER, COMPARATIVE STUDY OF BEVACIZUMAB (BEV)-BASED THERAPY IN PEDIATRIC PATIENTS WITH NEWLY DIAGNOSED HIGH-GRADE GLIOMA (HGG)
Bibliographic record
Abstract
HERBY (BO25041/NCT01390948) aimed to evaluate the efficacy and safety of BEV in addition to standard-of-care therapy (radiotherapy [RT]/temozolomide [TMZ]) in pediatric/adolescent patients with newly diagnosed HGG. Patients (≥3–<18 years) had HGG (supratentorial/infratentorial cerebellar/cerebellar peduncular); patients with gliomatosis cerebri or multifocal/metastatic HGGs were excluded. Randomization was stratified by age, surgery, and HGG grade. Diagnosis was confirmed before study entry by central pathology review. Histone status was determined. 121 patients (RT/TMZ n=59; BEV+RT/TMZ n=62; median age 11.0 years; <13 years, n=81; ≥13 years, n=40; 69% grade IV HGG; 50% had a total/near-total resection) were enrolled (October 2011–February 2015; 70 centers [Europe/Australia/Canada]). For RT/TMZ and BEV+RT/TMZ, respectively: 89.8% and 95.2% completed ≥90% of planned RT, and 81.4% and 85.5% completed ≥90% of planned TMZ (concurrent phase); 42.4% and 32.3% completed 12 TMZ cycles in the adjuvant phase. Median duration of survival follow-up: 15.2 months (RT/TMZ) and 16.2 months (BEV+RT/TMZ). Event-free survival (EFS) by central review (primary endpoint) was not significantly different between treatment arms (hazard ratio [HR]=1.44; 95% confidence interval [CI] 0.90–2.30; p=0.13 [log-rank test]). Similar results were observed in subgroup analyses of EFS by age/HGG grade/surgery/HGG location/histone status. Investigator-assessed EFS was also comparable (HR=1.49; 95% CI 0.92–2.40). The 1-year EFS rate was 48% (95% CI 35–61) and 38% (95% CI 26–51) for RT/TMZ versus BEV+RT/TMZ. There was no difference in overall survival (HR=1.23; 95% CI 0.72–2.09; interim assessment). No new safety signals were identified. For RT/TMZ versus BEV+RT/TMZ, respectively: the incidence of grade 3–5 adverse events (AEs) was 68% vs 70%; 0% vs 13% of patients had grade ≥3 proteinuria; 5% vs 22% of patients discontinued treatment due to toxicity (20% discontinued BEV). The addition of BEV to standard-of-care RT/TMZ did not improve EFS (central review) in pediatric patients with newly diagnosed HGG.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.004 | 0.001 |
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 source (direct Gemma or distilled Codex), 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".