Randomized phase II study of the x-linked inhibitor of apoptosis (XIAP) antisense AEG35156 in combination with sorafenib in patients with advanced hepatocellular carcinoma (HCC).
Bibliographic record
Abstract
4105 Background: XIAP inhibits caspases which are proteases responsible for apoptotic cell death. It is highly expressed in HCC. AEG35156 is a second generation antisense oligonucleotide targeting XIAP mRNA, thus lowers the apoptotic threshold of cancer cells. It also accumulates in the liver. This study is designed to assess the added benefit of combining AEG35156 with sorafenib. Methods: Patients with histologically or clinically diagnosed (AASLD criteria) HCC who had failed or were unsuitable for resection or ablative therapies were randomized (2:1) to receive either weekly injection of AEG35156 300mg in combination with sorefanib 400mg BID or sorefanib alone. The primary end point was progression-free survival (PFS). Other endpoints were overall survival (OS), response rates and safety. Results: 51 patients were recruited. 48 patents were evaluable. There were 31 patients in the combination arm and 17 in the control arm. The median age was 60. 88% of patients were male. 81% of patients were hepatitis B carrier. 90% of patients belong to Child-Pugh class A. The median follow-up was 16.2 months. The PFS for the combination arm was 4.0 months (95% CI: 1.2-4.1) and 2.6 months for control arm. The OS for the combination arm was 6.5 months (95% CI: 3.9-11.5) and 5.4 months for the control arm. There were 3 partial responders (Choi’s criteria) in the combination arm (10%, 95% CI: 3-27%) and none (0%) in the control arm. Patients who had the study treatment interrupted (PFS 4.0, 95% CI: 2.4-5.4) or had dose modification (PFS 4.45, 95% CI: 1.0-6.5) according to protocol did significantly better than those who had no dose reduction (PFS 1.2, 95% CI: 1.2-4.0) and those in the control arm (PFS 2.6, 95% CI: 1.2-5.4). This also applies to OS. Regarding toxicities, there were one AEG35156 related serious adverse event (SAE) of hypersensitivity and two sorafenib related gastrointestinal SAE. Conclusions: AEG35156 in combination with Sorafenib was well tolerated in patients with advanced HCC. Dose reduced AEG35156 in combination with sorafenib have shown more activity than sorafenib alone and warrants further investigation.
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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) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.003 | 0.001 |
| Bibliometrics | 0.001 | 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) | 0.007 | 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".