Overview of Arterial Thromboembolic Events (ATEs) in AVAglio, a Randomized, Placebo-controlled Phase III Trial of Bevacizumab, Radiotherapy and Temozolomide (BEV+RT/TMZ) for Newly Diagnosed Glioblastoma (S22.003)
Bibliographic record
Abstract
OBJECTIVE: To examine the incidence of ATEs in AVAglio. BACKGROUND: A significant PFS improvement (co-primary endpoint) was achieved in patients treated with BEV+RT/TMZ versus placebo (Plb+RT/TMZ). AVAglio safety data are presented, with a focus on ATEs. DESIGN/METHODS: Patients (蠅18 years/histologically confirmed glioblastoma) received BEV+RT/TMZ or Plb+RT/TMZ (6wks). After a 28-day break, patients received BEV+TMZ or Plb+TMZ (x6), then BEV or Plb until progression/unacceptable toxicity. Adverse events (AEs) of special interest for BEV were predefined. Statistical analyses: exploratory, non-protocol specified. RESULTS: Safety population: n=461 BEV+RT/TMZ; n=450 Plb+RT/TMZ. BEV or Plb administrations: median 19.0 (range 1-59) vs 12 (range 1-63) infusions, respectively. For BEV+RT/TMZ versus Plb+RT/TMZ, respectively: grade 蠅3 AEs were 66.8% vs 51.3%; grade 蠅3 AEs of special interest for BEV were 32.5% vs 15.8%; ATEs (any grade) were 5.9% (27/461 patients) vs 1.6% (7/450); grade 蠅3 ATEs were 4.8% (22/461) and 1.3% (6/450). Of the latter, 19/22 (86.4%) and 3/6 (50%) patients had 蠅1 co-morbidity risk factor. Two fatal ATEs occurred: myocardial infarction (BEV+RT/TMZ); cerebrovascular accident (Plb+RT/TMZ). ATE event rates were similar between arms until approximately 12 months, after which the rate in the BEV+RT/TMZ arm increased. Grade 蠅3 ATEs resolved in 15/22 (68%; BEV+RT/TMZ; 10/15 with sequelae) and 3/6 (50%; Plb+RT/TMZ; 2/3 with sequelae) patients. Most ATEs were classified as stroke (19/27 BEV+RT/TMZ; 6/7 Plb+RT/TMZ). Eleven strokes occurred in patients <65 years in the BEV+RT/TMZ arm (seven following 1.2-1.7 years of treatment without progression), nine of which resolved. Nine grade 蠅3 ATEs (BEV+RT/TMZ) occurred in patients 蠅65 years (vs 0 with Plb+RT/TMZ), five with a history of hypertension. In patients who experienced ATEs, median OS was 25.0 (BEV+RT/TMZ; n=27) and 11.2 months (Plb+RT/TMZ; n=7). CONCLUSION: More ATEs were reported in the BEV+RT/TMZ versus Plb+RT/TMZ arm. ATEs in the BEV+RT/TMZ arm tended to occur late in the study and may be related to prolonged treatment duration/co-morbidities, however the majority resolved (two-thirds with sequelae). Study supported by: F. Hoffmann-La Roche Ltd
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.004 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.002 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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 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".