A randomized trial of denosumab (AMG 162) versus intravenous (IV) bisphosphonates (BP) in cancer patients (pts) with bone metastases (BM) on established IV BP and evidence of elevated bone resorption
Bibliographic record
Abstract
8562 Background: Pts on established (≥ 8 weeks) IV BP who have elevated bone resorption markers, especially urinary N-telopeptide (uNTx), are at increased risk for skeletal related events (Coleman, J Clin Oncol 2005). Denosumab, a fully human monoclonal antibody, inhibits osteoclastic bone resorption by binding and neutralizing RANK ligand, a key mediator of osteoclast differentiation and function. Denosumab efficacy and safety were evaluated in a phase 2, randomized, open label, active-controlled study in advanced cancer pts with BM and elevated levels of uNTX despite established IV BP therapy. We report preliminary results from an interim analysis of 49 pts at week 13. Methods: Eligible pts (≥18 yrs old with solid tumor [except lung] or multiple myeloma [MM]; confirmed BM; screening uNTx > 50 nM BCE/mM creatinine [Cr]; on IV BP for ≥ 8 weeks before randomization) are stratified by baseline uNTx (50–100, >100) and tumor type. Pts are randomized to 1 of 3 arms: IV BP every 4 weeks (Q4W) or 180 mg denosumab given subcutaneously Q4W or Q12W. The primary endpoint is the proportion (%) of pts with uNTx < 50 nM BCE/mM Cr at week 13. Enrollment is ongoing (planned N = 135). Results: The mean (range) age of all pts in the analysis (33 denosumab; 16 BP) was 62.5 (39, 81) yrs; 96% had > 2 BM. The median time on prior IV BP (mostly zoledronic acid) was 5.1 months. Tumors included prostate (n = 24), breast (n = 20), other/MM (n = 5). The % of pts with uNTx < 50 nM BCE/mM Cr at week 13 was greater with denosumab (pooled arms) than IV BP: 76% (95% CI: 60.3, 91.2) vs 38% (95% CI: 18.5, 61.4; P = .015 Cochran-Mantel-Haenzel), respectively. No treatment-related serious adverse events (SAEs) were reported. Commonly reported AEs in the denosumab arms included nausea, peripheral edema, anemia, bone pain, and constipation. At data cutoff, 10 deaths (6/33 denosumab, 4/16 BP) had occurred on-study. Conclusions: These interim data suggest that denosumab normalizes uNTx more frequently than IV BP in pts with elevated uNTx despite 8 weeks of IV BP, across all tumor types. The AE profile of denosumab appeared similar to that of cancer pts undergoing treatment. [Table: see text]
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How this classification was reachedexpand
Direct model labels (unvalidated)
Per-model category and study-design labels from the labeling rounds. They are machine output, unvalidated, and the disagreement between models ships as data. No study design here is MEDLINE-validated yet.
| Model arm | Categories | Study design | Confidence |
|---|---|---|---|
| gemma | no category Domain: not available · Genre: Empirical About the Canadian research system: no · About a Canadian topic: no | Randomized trial | low |
| gpt | no category Domain: not available · Genre: Empirical About the Canadian research system: no · About a Canadian topic: no | Randomized trial | low |
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) | 0.003 | 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) | 0.009 | 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, unvalidatedLabeled directly by 2 models reading the full record.
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".