First-line randomized phase II study of gemcitabine/cisplatin plus apatorsen or placebo in patients with advanced bladder cancer: The International Borealis-1 trial.
Bibliographic record
Abstract
4503 Background: Heat shock protein 27 (Hsp27) is over-expressed in bladder cancer (BC) and postulated to increase tumor growth, metastasis, and chemotherapy resistance. Apatorsen (A; OGX-427), a novel antisense oligonucleotide, inhibits Hsp27 production and can potentially enhance the efficacy of chemotherapy. This trial was designed to evaluate efficacy and safety of A in combination with gemcitabine and cisplatin (GC) in patients (pts) with advanced BC. Methods: Chemotherapy naïve pts with advanced BC were randomized to GC+A 600 mg, GC+A 1000 mg, or GC + placebo. Pts were stratified by Karnofsky performance status (KPS) and visceral disease. The primary endpoint was overall survival (OS). Prognostic sub-groups were retrospectively evaluated using multiple variable modeling and hierarchical step down. A post hoc analysis was performed to explore the hypothesis that Hsp27 inhibition might be relevant to OS in poor prognosis disease. Results: A total of 179 pts were randomized/treated. Median OS was 15.2 months (m). When compared to GC + placebo, GC+A 600 demonstrated improved OS and PFS (OS HR = 0.856 and PFS HR = 0.830) versus GC+A 1000 (OS HR = 0.898; PFS HR = 0.927). Results from the post hoc model revealed that KPS, liver mets, alk phos, and hemoglobin were prognostic. A median prognostic score dichotomized pts into poor and good prognosis groups (50% each group). Pts with poor prognosis treated with GC+A 600 had a greater reduction in risk of death (HR = 0.717) than pts with good prognosis (HR = 1.44). The most significant prognostic factor was KPS ≤ 80% (35% pts in GC+A 600 vs GC) resulting in HR = 0.50 in favor of GC+A 600. Overall treatment was well tolerated. Most common Grade ≥ 3 adverse events (AEs) were neutropenia, anemia, thrombocytopenia and hypertension. Frequency of ≥ 3 Grade toxicities were: 89% (GC), 93% (GC+A 600) and 95% (GC+A 1000). GC+A 1000 had a higher treatment discontinuation rate due to AEs. Conclusions: Advanced BC pts with poor prognosis benefited from apatorsen 600mg combined with first line GC. Apatorsen may be impacting the intrinsic biology of patients with poor risk factors. Further evaluation is warranted in this pt population. Clinical trial information: NCT01454089.
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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 | 0.002 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.004 | 0.002 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.004 |
| Insufficient payload (model declined to judge) | 0.010 | 0.002 |
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".