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.
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.
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.
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.
European urology. 2024 Sep 05 [Epub ahead of print]
Andrew J Armstrong, Oliver Sartor, Johann de Bono, Kim Chi, Karim Fizazi, Bernd J Krause, Ken Herrmann, Kambiz Rahbar, Scott T Tagawa, Fred Saad, Tomasz M Beer, Jiwen Wu, Osvaldo Mirante, Michael J Morris
Duke Cancer Institute Center for Prostate and Urologic Cancers, Departments of Medicine, Surgery, Pharmacology and Cancer Biology, Duke University, Durham, NC, USA., Department of Medical Oncology, Mayo Clinic, Rochester, MN, USA., The Institute of Cancer Research and The Royal Marsden Hospital, London, UK., Division of Medical Oncology, University of British Columbia, Vancouver, BC, Canada., Cancer Medicine Department, Gustave Roussy Institute, University of Paris Saclay, Villejuif, France., Department of Nuclear Medicine, Rostock University Medical Center, Rostock, Germany., Clinic for Nuclear Medicine, University Hospital Essen, Essen, Germany., Department of Nuclear Medicine, University Hospital Münster, Münster, Germany., Division of Hematology and Medical Oncology, Weill Cornell Medicine, New York, NY, USA., Urology Department, University of Montreal Hospital Center, University of Montreal, Montreal, QC, Canada., Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA., Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA., Advanced Accelerator Applications, a Novartis company, Geneva, Switzerland., Genitourinary Oncology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA. Electronic address: .