Final overall survival and safety analyses of the phase III PSMAfore trial of [177Lu]Lu-PSMA-617 versus change of androgen receptor pathway inhibitor in taxane-naive patients with metastatic castration-resistant prostate cancer
Bibliographic record
Abstract
Background In PSMAfore, [ 177 Lu]Lu-PSMA-617 ( 177 Lu-PSMA-617) prolonged radiographic progression-free survival (rPFS) in taxane-naive patients with metastatic castration-resistant prostate cancer (mCRPC), with a favourable safety profile, versus a change in androgen receptor pathway inhibitor (ARPI). We report the final overall survival (OS) analysis and updated safety data. Patients and methods PSMAfore (NCT04689828) was an open-label, international, phase III trial. Patients with prostate-specific membrane antigen (PSMA)-positive mCRPC who had experienced disease progression once on a previous ARPI and were candidates for ARPI change were randomized 1 : 1 to 177 Lu-PSMA-617 or ARPI change to abiraterone or enzalutamide. Crossover from ARPI change to 177 Lu-PSMA-617 was allowed after centrally confirmed radiographic progression. Endpoints included rPFS (primary), OS (key secondary), and safety (secondary). Results Patients were randomized to 177 Lu-PSMA-617 or ARPI change ( n = 234 each): 141/234 participants (60.3%) randomized to ARPI change crossed over (75.4% of those with centrally confirmed radiographic progression). The median OS was 24.48 months [95% confidence interval (CI) 19.55-28.94 months] with 177 Lu-PSMA-617 versus 23.13 months (95% CI 19.61-25.53 months) with ARPI change [hazard ratio (HR) 0.91, 95% CI 0.72-1.14, P = 0.20] based on the intention-to-treat (ITT) principle; the crossover-adjusted OS HR by inverse probability of censoring weighting modelling was 0.59 (95% CI 0.38-0.91). For 177 Lu-PSMA-617 versus ARPI change, exposure-adjusted incidences of grade ≥3 and serious treatment-emergent adverse events were 60.8 versus 85.1 and 32.5 versus 49.9 per 100 patient-treatment years, respectively. Dry mouth occurred in 135/227 participants (59.5%; 2/227 grade ≥3) and anaemia in 62/227 (27.3%; 14/227 grade ≥3) in the 177 Lu-PSMA-617 arm. Conclusions OS analyses did not show a statistically significant difference between the 177 Lu-PSMA-617 and ARPI arms based on the ITT principle; results were likely confounded by the high rate of crossover. The safety profile of 177 Lu-PSMA-617 was favourable with no new safety signals identified.
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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 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.004 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.004 |
| Insufficient payload (model declined to judge) | 0.004 | 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".