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Item does not contain fulltext BACKGROUND: In VISION, the prostate-specific membrane antigen (PSMA)-targeted radioligand therapy lutetium-177 [(177)Lu]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. METHODS: 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 [(177)Lu]Lu-PSMA-617 plus protocol-permitted standard of care ([(177)Lu]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 [(177)Lu]Lu-PSMA-617 group received intravenous infusions of 7·4 gigabecquerel (GBq; 200 millicurie [mCi]) [(177)Lu]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. FINDINGS: Between June 4, 2018, and Oct 23, 2019, 831 patients were enrolled, of whom 581 were randomly assigned to the [(177)Lu]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 [(177)Lu]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% CI 10·3-13·2) in the [(177)Lu]Lu-PSMA-617 group and 6·8 months (5·2-8·5) in the control group (hazard ratio [HR] 0·50, 95% CI 0·40-0·62). Time to worsening was delayed in the [(177)Lu]Lu-PSMA-617 group versus the control group for FACT-P score (HR 0·54, 0·45-0·66) and subdomains, BPI-SF pain intensity score (0·52, 0·42-0·63), and EQ-5D-5L utility score (0·65, 0·54-0·78). Grade 3 or 4 haematological adverse events included decreased haemoglobin (80 [15%] of 529 assessable patients who received [(177)Lu]Lu-PSMA-617 plus standard of care vs 13 [6%] of 205 who received standard of care only), lymphocyte concentrations (269 [51%] vs 39 [19%]), and platelet counts (49 [9%] vs five [2%]). Treatment-related adverse events leading to death occurred in five (1%) patients who received [(177)Lu]Lu-PSMA-617 plus standard of care (pancytopenia [n=2], bone marrow failure [n=1], subdural haematoma [n=1], and intracranial haemorrhage [n=1]) and no patients who received standard of care only. INTERPRETATION: [(177)Lu]Lu-PSMA-617 plus standard of care delayed time to worsening in HRQOL and time to skeletal events compared with standard of care alone. These findings support the use of [(177)Lu]Lu-PSMA-617 in patients with metastatic castration-resistant prostate cancer who received previous androgen receptor pathway inhibitor and taxane treatment. FUNDING: Advanced Accelerator Applications (Novartis). 01 juni 2023

Development of a simple and accurate technique for detecting active inflammation in the joints and other tissues of patients with inflammatory disorders is an unmet need in rheumatic diseases. This study is a preliminary assessment of the safety and usage of a radiopharmaceutical, FolateScan (Technetium-99m EC20; 99mTc-EC20), for detecting disease activity in patients with rheumatoid arthritis.EC20 is a folate-targeted diagnostic radiopharmaceutical which binds to the folate receptor and is preferentially taken up by activated macrophages. In this open-label, cross-sectional study, a total of 40 patients with RA (26 with one or more swollen joints, 14 with clinically quiescent joint disease; 0/66 joint count) as well as 6 patients with osteoarthritis, 12 patients with other inflammatory conditions and 5 healthy subjects received 0.1 mg of EC20 labeled with 20-25mCi of technetium-99m. Disease activity was scored in each joint and other target tissues by a radiologist blinded to the clinical assessment, and results were compared to the rheumatologist's physical examination, which served as the test standard.The 40 patients (78% female) with RA had a mean age of 56.9 years. Assessment of uptake of 99mTc-EC20 in joints of patients with RA based on image analysis was compared to the clinical examination. FolateScan detected more actively involved joints in 27 patients (68%) than joints recorded as "swollen", and more actively involved joints in 25 patients (63%) than joints recorded as "painful and/or swollen". The number of swollen joints by clinical exam was correlated with ESR (r=0.43; p=0.006) and C-rp (r=0.35; p=0.03). The number of actively involved joints by FolateScan was also correlated with ESR (r=0.47; p=0.002) and C-rp (r=0.36; p=0.02). Joint uptake was also seen in patients with osteoarthritis.FolateScan is a potentially useful tool for detection of disease activity in patients with RA and may be more sensitive than the physical examination.