A randomized phase 2 study investigating 3 dosing regimens of radium-223 dichloride (Ra-223) in bone metastatic castration-resistant prostate cancer (mCRPC).
Bibliographic record
Abstract
5008 Background: Ra-223, standard dose (SD) 55 kBq/kg q4w for 6 cycles improved overall survival (OS) and delayed time to symptomatic skeletal events (SSEs) in patients (pts) with mCRPC and bone metastases in the ALSYMPCA study (Parker C, N Engl J Med. 2013;369(3):213-23). The current study investigated different Ra-223 treatment regimens in a similar patient population. Methods: Pts with bone mCRPC were randomized 1:1:1 to Ra-223 SD or Ra-223 high dose (HD) 88 kBq/kg q4w for up to 6 cycles, or to Ra-223 SD extended (EXT) q4w for up to 12 cycles. The primary objective was to compare SSE-free survival (SSE-FS) between HD and SD, and EXT and SD. Hypothesis testing was performed at a 2-sided alpha level of 0.20 with no adjustment for multiplicity. Results: 391 pts were randomized; baseline characteristics were well balanced. No statistically significant differences in SSE-FS were observed between Ra-223 SD and HD [median 12.3 vs 12.9 months, hazard ratio (HR) 1.06, 80% CI 0.88–1.27, p = 0.70] or Ra-223 SD and EXT [median 13.2 vs 10.8 months, HR 1.26, 80% CI 0.94–1.69, p = 0.31]. Median OS was 15.8, 16.0 and 14.4 months in the SD, HD and EXT arms, respectively. A total of 370 pts received Ra-223 with a median number of doses of 6 in each arm. The most frequent treatment emergent adverse events (TEAEs) were fatigue, anemia and nausea. Grade ≥3 TEAEs were noted in 34%, 48% and 53% of pts in the SD, HD and EXT arms, respectively. The most frequent grade ≥3 TEAEs overall were anemia (13%), bone pain (5%), thrombocytopenia (4%) and hypertension (4%). TEAEs leading to permanent discontinuation occurred in 9%, 16% and 17% of pts in the SD, HD and EXT arms, respectively. Conclusions: No statistically significant differences in SSE-FS were noted between Ra-223 SD and HD or Ra-223 SD and EXT. However, HD and EXT arms had a higher incidence of grade ≥3 TEAEs than the SD arm. The study supports the currently approved dose and schedule of Ra-223. Clinical trial information: NCT02023697.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.007 | 0.008 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".