ET-12 * PHASE II STUDY OF ONARTUZUMAB PLUS BEVACIZUMAB VERSUS PLACEBO PLUS BEVACIZUMAB IN PATIENTS WITH RECURRENT GLIOBLASTOMA
Bibliographic record
Abstract
BACKGROUND: Glioblastomas are highly vascularized with elevated VEGF expression and have been shown to respond to the anti-VEGF antibody bevacizumab. High MET expression has been associated with shorter progression-free survival (PFS) in glioblastomas (Pierscianek, et al. Brain Pathol 2013). This phase II study investigated the monovalent MET inhibitor, onartuzumab, plus bevacizumab (Ona + Bev) versus placebo plus bevacizumab (Pl + Bev) in recurrent glioblastoma. METHODS: Bevacizumab-naïve patients with glioblastoma at first recurrence following chemoradiation were randomized 1:1 to receive Ona (15mg/kg, q3w) + Bev (15mg/kg, q3w) or Pl + Bev until disease progression. Enrollment onto a third arm, Ona + Pl, was put on hold during assessment of safety data and was subsequently closed due to study conduct concerns (data not presented). Primary endpoint: PFS by RANO criteria (ITT and MET biomarker-positive subpopulations). Secondary endpoints: overall survival, objective response rate, duration of response, and safety. RESULTS: In the 129 patients enrolled (Ona + Bev n = 64, Pl + Bev n = 65) baseline characteristics were balanced; median age was 57 years; 43.4% had Karnofsky performance status 90-100%; 87.6% had measurable disease at baseline. Median number of bevacizumab cycles: 5 for Ona + Bev, 6 for Pl + Bev; median onartuzumab cycles, 4; median placebo cycles, 6. Grade ≥3 adverse events (AEs) were reported in 38.5% of Ona + Bev and 35.9% of Pl + Bev patients; serious AEs were reported in 30.8% and 29.7%, respectively. Grade 5 AEs: Ona + Bev n = 2 intestinal perforation; Pl + Bev n = 1 intracranial hemorrhage. AEs leading to study drug withdrawal were seen in 10.8% of Ona + Bev and 6.3% of Pl + Bev patients. AEs (all grades) with a difference in incidence of ≥10% between arms included peripheral edema (44.6% Ona + Bev, 14.1% Pl + Bev), hypertension (12.3% Ona + Bev, 32.8% Pl + Bev) and hypoalbuminemia (12.3% Ona + Bev, 1.6% Pl + Bev). Efficacy data are pending. CONCLUSION: The AEs observed were consistent with previous safety profiles for onartuzumab and bevacizumab with no new safety signals. Efficacy data will be presented.
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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 | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.003 | 0.002 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.003 |
| Insufficient payload (model declined to judge) | 0.005 | 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".