Hypocalcemia in patients with metastatic bone disease receiving denosumab.
Bibliographic record
Abstract
9628 Background: Patients (pts) with metastatic bone disease (MBD) are at risk of skeletal-related events (SREs). Potent antiresorptives reduce the risk of SREs, by inhibiting cancer-induced bone destruction, which also reduces release of skeletal calcium (Ca) into the bloodstream. Hypocalcemia (hypoCa) may occur if Ca and vit D intake is inadequate while taking antiresorptive agents. A combined analysis of 3 phase III trials in pts with MBD showed denosumab (DMAb) was superior to zoledronic acid (ZA) in preventing SREs. The overall safety profiles were similar; hypoCa was more common with DMAb (9.6%) than ZA (5.0%). Characteristics of hypoCa events in DMAb pts in these clinical trials and from post marketing adverse event (AE) reports are presented. Methods: Pts with solid tumors or multiple myeloma and MBD were randomized (1:1) to DMAb 120 mg SC or ZA 4 mg IV (adjusted for renal function) every 4 weeks (Q4W). Pts were advised to take daily Ca (≥ 500 mg) and vit D (≥ 400 IU); intake was collected by pt report. Albumin-corrected serum Ca was measured Q4W by central lab. HypoCa events were collected as decreases in serum Ca per central lab and investigator-reported AEs. Post marketing data from spontaneous reports of hypoCa to the sponsor's global safety department (AGS) were reviewed. Results: In the 3 trials, 2841 pts received DMAb and 2836 pts received ZA. The median Ca levels for both treatment groups were similar over time. Among DMAb pts, hypoCa was most common within 6 months of starting treatment and was more common in pts who did not report use of Ca and vit D vs those who did (15.8% vs 8.7%). Grade 3 or 4 (< 7 mg/dL; < 1.75 mmol/L) decreases in serum Ca were reported in 3.1% of DMAb pts and 1.3% of ZA pts. No fatal cases of hypoCa were reported in the trials. From May to Nov 2012, 37 cases of severe symptomatic hypoCa (seizures, tetany, prolonged QTc, altered mental state) were reported to AGS; fatal outcomes were reported for 3 other pts with advanced cancers and various comorbidities. Conclusions: HypoCa is a known risk with antiresorptive therapy, including DMAb 120 mg. HypoCa occurred less often in pts who reported taking Ca and vit D. HypoCa should be corrected prior to starting DMAb and Ca monitored during treatment. Pts should take adequate Ca and vit D while receiving DMAb. Clinical trial information: NCT00321464, NCT00321620, and NCT00330759.
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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 | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".