Radium-223 in an international early access program (EAP): Effects of concomitant medication on overall survival in metastatic castration-resistant prostate cancer (mCRCP) patients.
Bibliographic record
Abstract
5034 Background: The pivotal ALSYMPCA study reported improved overall survival (OS) in bone symptomatic mCRPC patients (pts) treated with radium-223 (Ra-223) vs placebo (median 14.9 vs 11.6 months [mos], HR = 0.70). Data from 696 EAP pts recruited from 14 countries (Europe, Canada, Israel) are presented. Methods: In this prospective phase IIIb study, mCRPC pts with symptomatic or asymptomatic bone metastases (no visceral disease) received Ra-223, 50 kBq/kg (iv injection) every 4 weeks for 6 cycles. Primary endpoints were safety and OS. The effects of concomitant medications, baseline (BL) pain, alkaline phosphatase (ALP) and ECOG PS on OS were assessed. Results: 696 pts were treated; 58% received all 6 Ra-223 injections. At BL: median age was 72 years; 88% of pts were ECOG PS 0–1; pain was reported as: no pain, mild-moderate, and severe in 21%, 52%, and 27% respectively. 60% of pts received prior therapy with docetaxel. For pts treated with concomitant therapy: 22% were with abiraterone; 20% with denosumab; 18% with bisphosphonates and 4% with enzalutamide. Grade 3/4 AEs were reported in 38% of pts; 21% discontinued Ra-223 due to AEs. At the time of analysis median OS was 16 mos [13–not estimated (NE)]. Median time to first SSE was 18 mos [17–NE]; 24% of pts had ≥ 50% confirmed ALP decrease from BL; 8% had > 50% confirmed PSA decrease from BL. In post hoc analyses OS was statistically significantly longer in pts with BL: ALP <220 U/L vs ≥ 220 U/L; ECOG PS 0–1 vs ≥ 2; no pain vs mild-moderate vs severe; concomitant denosumab; concomitant abiraterone (Table). Conclusions: In Ra-223 treated pts, OS appeared to be better in those treated concomitantly with denosumab or abiraterone. Significantly longer OS was observed in pts with a good ECOG PS, no pain and low ALP. Clinical trial information: 2012-000075-16. Characteristic Pts, n Median OS, mos (95% CI) Log-rank p-value Concomitant denosumab Yes 138 NA (15–NE) 0.00940 No 558 13 (12–NE) Concomitant abiraterone Yes 156 NA (16–NE) < 0.0001 No 540 14 (12–16) ALP < 220U/L 431 NA (NE) < 0.0001 ≥ 220U/L 263 10 (9–11) ECOG-PS 0-1 609 17 (14–NE) < 0.0001 ≥ 2 87 7 (5–11) Pain No 146 NA (16–NE) 0.00018* Mild-moderate 360 15 (13–NE) Severe 163 11 (8–12) *No vs all pain. NA, not available.
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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 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| 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) | 0.001 | 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".