TY  - JOUR
AU  - Fizazi, Karim
AU  - Herrmann, Ken
AU  - Krause, Bernd J
AU  - Rahbar, Kambiz
AU  - Chi, Kim N
AU  - Morris, Michael J
AU  - Sartor, Oliver
AU  - Tagawa, Scott T
AU  - Kendi, Ayse T
AU  - Vogelzang, Nicholas
AU  - Calais, Jeremie
AU  - Nagarajah, James
AU  - Wei, Xiao X
AU  - Koshkin, Vadim S
AU  - Beauregard, Jean-Mathieu
AU  - Chang, Brian
AU  - Ghouse, Ray
AU  - DeSilvio, Michelle
AU  - Messmann, Richard A
AU  - de Bono, Johann
TI  - Health-related quality of life and pain outcomes with [177Lu]Lu-PSMA-617 plus standard of care versus standard of care in patients with metastatic castration-resistant prostate cancer (VISION): a multicentre, open-label, randomised, phase 3 trial.
JO  - The lancet  / Oncology
VL  - 24
IS  - 6
SN  - 1470-2045
CY  - London
PB  - The Lancet Publ. Group
M1  - DKFZ-2023-01089
SP  - 597 - 610
PY  - 2023
AB  - In VISION, the prostate-specific membrane antigen (PSMA)-targeted radioligand therapy lutetium-177 [177Lu]Lu-PSMA-617 (vipivotide tetraxetan) improved radiographic progression-free survival and overall survival when added to protocol-permitted standard of care in patients with metastatic castration-resistant prostate cancer. Here, we report additional health-related quality of life (HRQOL), pain, and symptomatic skeletal event results.This multicentre, open-label, randomised, phase 3 trial was conducted at 84 cancer centres in nine countries in North America and Europe. Eligible patients were aged 18 years or older; had progressive PSMA-positive metastatic castration-resistant prostate cancer; an Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2; and had previously received of at least one androgen receptor pathway inhibitor and one or two taxane-containing regimens. Patients were randomly assigned (2:1) to receive either [177Lu]Lu-PSMA-617 plus protocol-permitted standard of care ([177Lu]Lu-PSMA-617 group) or standard of care alone (control group) using permuted blocks. Randomisation was stratified by baseline lactate dehydrogenase concentration, liver metastases, ECOG performance status, and androgen receptor pathway inhibitor inclusion in standard of care. Patients in the [177Lu]Lu-PSMA-617 group received intravenous infusions of 7·4 gigabecquerel (GBq; 200 millicurie [mCi]) [177Lu]Lu-PSMA-617 every 6 weeks for four cycles plus two optional additional cycles. Standard of care included approved hormonal treatments, bisphosphonates, and radiotherapy. The alternate primary endpoints were radiographic progression-free survival and overall survival, which have been reported. Here we report the key secondary endpoint of time to first symptomatic skeletal event, and other secondary endpoints of HRQOL assessed with the Functional Assessment of Cancer Therapy-Prostate (FACT-P) and EQ-5D-5L, and pain assessed with the Brief Pain Inventory-Short Form (BPI-SF). Patient-reported outcomes and symptomatic skeletal events were analysed in all patients who were randomly assigned after implementation of measures designed to reduce the dropout rate in the control group (on or after March 5, 2019), and safety was analysed according to treatment received in all patients who received at least one dose of treatment. This trial is registered with ClinicalTrials.gov, NCT03511664, and is active but not recruiting.Between June 4, 2018, and Oct 23, 2019, 831 patients were enrolled, of whom 581 were randomly assigned to the [177Lu]Lu-PSMA-617 group (n=385) or control group (n=196) on or after March 5, 2019, and were included in analyses of HRQOL, pain, and time to first symptomatic skeletal event. The median age of patients was 71 years (IQR 65-75) in the [177Lu]Lu-PSMA-617 group and 72·0 years (66-76) in the control group. Median time to first symptomatic skeletal event or death was 11·5 months (95
KW  - Male
KW  - Humans
KW  - Aged
KW  - Quality of Life
KW  - Prostatic Neoplasms, Castration-Resistant: drug therapy
KW  - Receptors, Androgen
KW  - Standard of Care
KW  - Androgen Receptor Antagonists: adverse effects
KW  - Pain: chemically induced
KW  - Taxoids
KW  - Antineoplastic Combined Chemotherapy Protocols: adverse effects
KW  - PSMA-617 (NLM Chemicals)
KW  - Receptors, Androgen (NLM Chemicals)
KW  - Androgen Receptor Antagonists (NLM Chemicals)
KW  - taxane (NLM Chemicals)
KW  - Taxoids (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:37269841
DO  - DOI:10.1016/S1470-2045(23)00158-4
UR  - https://inrepo02.dkfz.de/record/276405
ER  -