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 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) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.003 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.002 | 0.003 |
| Insufficient payload (model declined to judge) | 0.008 | 0.001 |
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".