Incidence of osteonecrosis of the jaw in patients receiving denosumab or zoledronic acid for bone metastases from solid tumors or multiple myeloma: Results from three phase III trials.
Bibliographic record
Abstract
9640 Background: In patients with metastatic bone disease (MBD), the use of antiresorptive therapies such as denosumab or zoledronic acid (ZA) reduces the risk of skeletal-related events but is associated with a small risk of osteonecrosis of the jaw (ONJ). Two phase 3 clinical trials of denosumab vs ZA in patients with MBD showed overall cumulative ONJ incidences to be 3.8% to 4.7% at approximately 5 years of treatment with denosumab across blinded and open-label extension phases. ONJ associated with ZA was only assessed in the blinded treatment phases, as patients switched to denosumab once superior efficacy was demonstrated. Here we report incidence rates of ONJ by first vs subsequent years of exposure for the blinded treatment phase of all three phase III clinical trials. Methods: Patients (n = 5,677) with bone metastases from solid tumors or multiple myeloma received either SC denosumab 120 mg and IV placebo or IV ZA 4 mg (adjusted for renal function) and SC placebo Q4W in the double-blinded treatment phase of each trial. Patients who received ≥ 1 active dose during the blinded treatment phase were included in this analysis for up to 44.5 months of denosumab exposure and 41.3 months of ZA exposure. Oral assessments were conducted at baseline and every 6 months thereafter by the investigator or other qualified examiner. Potential ONJ events were independently adjudicated by a blinded committee of experts. Results: The median (Q1, Q3) time to onset of ONJ was similar in both treatment groups (15.6 [9.5, 20.0] months for denosumab, 15.8 [11.0, 23.6] months for ZA). Cumulative incidence rates of ONJ during the blinded treatment phases for all three trials by patient-years of follow-up are shown below (Table). Conclusions: The incidence of ONJ increased with longer duration of antiresorptive exposure. There were no significant differences between treatment groups in ONJ incidence at year 1 or beyond. Clinical trial information: NCT00321464; NCT00330759; NCT00321620. [Table: see text]
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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 | 0.011 | 0.005 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.004 |
| Bibliometrics | 0.001 | 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 | 0.002 |
| Insufficient payload (model declined to judge) | 0.001 | 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".