A randomized trial comparing four-weekly versus 12-weekly administration of bone-targeted agents (denosumab, zoledronate, or pamidronate) in patients with bone metastases from either breast or castration-resistant prostate cancer.
Bibliographic record
Abstract
11501 Background: Defining the optimal dosing interval of commonly used bone-targeted agents (BTAs), such as denosumab and bisphosphonates, for patients with bone metastases remains an important clinical question. We performed a pragmatic randomised trial comparing the non-inferiority of 12- versus 4-weekly BTAs in patients with bone metastases from breast and prostate cancer. Methods: Patients with bone metastases, who were either BTA-naïve, or already receiving, denosumab, pamidronate or zoledronate were eligible. They were randomised to receive their chosen BTA every 12- or 4-weeks for one year. The primary endpoint was Health related quality of life (HRQL) (EORTC-QLQ-C30 Functional Domain - Physical Subdomain). Secondary endpoints included: pain (EORTC-QLQ-BM22 - pain domain), Global Health Status (EORTC-QLQ-C30), symptomatic skeletal events (SSE) rates and time to SSEs. Adverse events and toxicity profiles were also compared. Results: Of 263 patients (60.8% breast and 39.2% prostate), 130 (49.4%) were randomised to 12-weekly and 133 (50.6%) to 4-weekly therapy. 138 (52.5%) were bone-agent naïve. The BTAs included; denosumab (n=148, 56.3%), zoledronate (n=63, 24.0%) and pamidronate (n=52, 19.8%). Study-reported outcomes showed no significant difference in; HRQL-physical domain (median [range]: 0 [-86, 40] vs. 0 [-66, 53.3]), pain (median [range]: 0 [-66, 72] vs. 0 [-100, 88]), Global Health Status (median [range]: 0 [-100, 66.7] vs. 0 [-83, 33.3]), SSE rates (N [%]: 24 [18.5%] vs. 22 [16.5%]), 1-year SSE-free rate (median, range; 73.2% [63.6, 80.7] vs. 77.9% [69.1, 84.4]) between the 12- and 4-weekly arms, respectively. Subgroup analyses for BTA naïve and pre-treated patients, and for patients receiving denosumab, zoledronate and pamidronate, showed no significant difference between the 12- and 4-weekly arms. There was no significant difference in reported rates of renal impairment (2.3% vs. 3.0%), symptomatic hypocalcaemia (1.5% vs. 1.5%) or osteonecrosis of the jaw (0.8% vs. 0.8%). Conclusion: The findings of this trial are consistent with those previously reported for de-escalating zoledronate. This trial also included patients receiving de-escalated denosumab and pamidronate. While the results of the Swiss REDUSE trial are awaited, the data presented would suggest that de-escalation of all commonly used BTAs is a reasonable treatment option. Clinical trial information: NCT02721433.
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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 | 0.004 | 0.005 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.005 | 0.003 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.002 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.003 | 0.003 |
| Insufficient payload (model declined to judge) | 0.013 | 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".