Phase III study of lutetium-177-PSMA-617 in patients with metastatic castration-resistant prostate cancer (VISION).
Bibliographic record
Abstract
LBA4 Background: Despite recent therapeutic advances, metastatic castration-resistant prostate cancer (mCRPC) remains invariably fatal. Prostate-specific membrane antigen (PSMA) is highly expressed in mCRPC lesions. 177 Lu-PSMA-617 is a targeted radioligand therapy that delivers ß-particle radiation to PSMA-expressing cells and surrounding microenvironment. Method: VISION was an international, randomized, open-label phase III study evaluating 177 Lu-PSMA-617 in men with PSMA-positive mCRPC previously treated with next-generation androgen receptor signaling inhibition and 1–2 taxane regimens. PSMA positivity (threshold greater than liver) was determined by central review of 68 Ga-PSMA-11 scans. Patients were randomized 2:1 to 177 Lu-PSMA-617 (7.4 GBq every 6 weeks x 6 cycles) plus standard of care (SOC) versus SOC alone. SOC was investigator determined but excluded cytotoxic chemotherapy and radium-223. The alternate primary endpoints were radiographic progression-free survival (rPFS) using PCWG3 criteria by independent central review (ICR) and overall survival (OS). Under the null hypothesis, median rPFS was assumed to be 4 months and OS 10 months for 177 Lu-PSMA-617 + SOC for a hazard ratio (HR) of 1.00. Under the alternative hypothesis, median rPFS was assumed to be 6 months for a HR of 0.67 and median OS was assumed to be 13.7 months for a HR of 0.7306. Key secondary endpoints were objective response rate (ORR; RECIST v1.1), disease control rate (DCR), and time to first symptomatic skeletal event (SSE). Results: Between 4 June 2018 and 23 October 2019, 831 of 1179 screened patients were randomized 2:1 to receive 177 Lu-PSMA-617 + SOC (n = 551) or SOC only (n = 280). Median study follow-up was 20.9 months at the data cut-off (27 January 2021). Treatment groups were balanced in terms of demographics and baseline characteristics. 177 Lu-PSMA-617 + SOC significantly improved rPFS versus SOC alone (median rPFS, 8.7 vs 3.4 months; HR, 0.40 [99.2% CI: 0.29, 0.57]; p < 0.001, one-sided). The alternate primary endpoint of OS was also significantly improved versus SOC alone (median OS, 15.3 vs 11.3 months; HR, 0.62 [95% CI: 0.52, 0.74]; p < 0.001, one-sided). All key secondary endpoints were statistically significant between the treatment arms in favor of 177 Lu-PSMA-617 + SOC, including ICR-determined ORR (29.8% vs 1.7%), ICR-determined DCR (89.0% vs 66.7%) and time to first SSE (median time, 11.5 vs 6.8 months; HR, 0.50). While a higher rate of high-grade treatment-emergent adverse events was observed with 177 Lu-PSMA-617 (52.7% vs 38.0%), therapy was well tolerated. Conclusions: 177 Lu-PSMA-617 plus SOC treatment is a well-tolerated regimen that improves rPFS and prolongs OS compared with SOC alone in men with advanced-stage PSMA-positive mCRPC, supporting its adoption as a standard of care. Clinical trial information: NCT03511664.
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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 | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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) | 0.000 | 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".