Association of declining prostate-specific antigen levels with clinical outcomes in patients with metastatic castration-resistant prostate cancer receiving [(177)Lu]Lu-PSMA-617 in the phase 3 VISION trial Journal Article
| Authors: | Armstrong, A. J.; Sartor, O.; de Bono, J.; Chi, K.; Fizazi, K.; Krause, B. J.; Herrmann, K.; Rahbar, K.; Tagawa, S. T.; Saad, F.; Beer, T. M.; Wu, J.; Mirante, O.; Morris, M. J. |
| Article Title: | Association of declining prostate-specific antigen levels with clinical outcomes in patients with metastatic castration-resistant prostate cancer receiving [(177)Lu]Lu-PSMA-617 in the phase 3 VISION trial |
| Abstract: | Background and objective: The prognostic value of declining prostate-specific antigen (PSA) levels is under investigation in patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC) receiving PSMA-targeted radioligand therapy with [177Lu]Lu-PSMA-617 (177Lu-PSMA-617). This post hoc analysis of the phase 3 VISION trial aimed to evaluate associations between PSA decline and clinical and patient-reported outcomes in patients receiving 177Lu-PSMA-617. Methods: Of 831 enrolled patients with PSMA-positive progressive mCRPC treated previously with one or more androgen receptor pathway inhibitors and one to two taxanes, 551 were randomised to 177Lu-PSMA-617 plus protocol-permitted standard of care (SoC). Radiographic progression-free survival, overall survival, radiographic objective response rate, and patient-reported health-related quality of life (HRQoL) and pain were analysed in subgroups of patients categorised by the magnitude of unconfirmed PSA decline from baseline. Key findings and limitations: Patients randomised to 177Lu-PSMA-617 with the best PSA declines of ≥0–<50% (96/551 [17%]), ≥50–<90% (152/551 [28%]), and ≥90% (83/551 [15%]) up to and including week 12 had 61%, 72%, and 88% reduced risks of radiographic disease progression or death, and 51%, 70%, and 87% reduced risks of death, respectively, versus those with increased PSA levels (160/551 [29%]), based on hazard ratios in a multivariate Cox proportional hazard model. In patients with greater PSA declines, radiographic responses were more frequent and median time to worsening in HRQoL and pain scores were longer. Conclusions and clinical implications: The magnitude of PSA decline was associated with improvement in clinical and patient-reported outcomes in patients with mCRPC receiving 177Lu-PSMA-617 plus SoC in VISION. PSA decline therefore appears to have a prognostic value during 177Lu-PSMA-617 treatment in this population. © 2024 The Author(s) |
| Keywords: | controlled study; treatment outcome; aged; middle aged; major clinical study; overall survival; clinical trial; radiopharmaceuticals; prostate specific antigen; metastasis; progression free survival; quality of life; randomized controlled trial; radiotherapy; pathology; prostate-specific antigen; blood; neoplasm metastasis; radiopharmaceutical agent; phase 3 clinical trial; radioisotope; radioisotopes; prognostic biomarker; castration resistant prostate cancer; dipeptides; progression-free survival; abiraterone; clinical outcome; single heterocyclic rings; heterocyclic compounds, 1-ring; patient-reported outcome; brief pain inventory; lutetium; randomised controlled trial; dipeptide; enzalutamide; metastatic castration-resistant prostate cancer; humans; human; male; article; prostatic neoplasms, castration-resistant; metastatic castration resistant prostate cancer; radioligand therapy; european quality of life 5 dimensions questionnaire; vipivotide tetraxetan lutetium lu 177; functional assessment of cancer therapy prostate; <sup>177</sup>lu-psma-617 |
| Journal Title: | European Urology |
| Volume: | 86 |
| Issue: | 6 |
| ISSN: | 0302-2838 |
| Publisher: | Elsevier Science, Inc. |
| Date Published: | 2024-12-01 |
| Start Page: | 552 |
| End Page: | 562 |
| Language: | English |
| DOI: | 10.1016/j.eururo.2024.08.021 |
| PUBMED: | 39242323 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Erratum issued, see DOI: 10.1016/j.eururo.2025.03.008 -- Source: Scopus |
