000276405 001__ 276405 000276405 005__ 20240229162338.0 000276405 0247_ $$2doi$$a10.1016/S1470-2045(23)00158-4 000276405 0247_ $$2pmid$$apmid:37269841 000276405 0247_ $$2ISSN$$a1470-2045 000276405 0247_ $$2ISSN$$a1474-5488 000276405 0247_ $$2altmetric$$aaltmetric:149193519 000276405 037__ $$aDKFZ-2023-01089 000276405 041__ $$aEnglish 000276405 082__ $$a610 000276405 1001_ $$aFizazi, Karim$$b0 000276405 245__ $$aHealth-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. 000276405 260__ $$aLondon$$bThe Lancet Publ. Group$$c2023 000276405 3367_ $$2DRIVER$$aarticle 000276405 3367_ $$2DataCite$$aOutput Types/Journal article 000276405 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1686034026_3286 000276405 3367_ $$2BibTeX$$aARTICLE 000276405 3367_ $$2ORCID$$aJOURNAL_ARTICLE 000276405 3367_ $$00$$2EndNote$$aJournal Article 000276405 520__ $$aIn 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% CI 10·3-13·2) in the [177Lu]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 [177Lu]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 [177Lu]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 [177Lu]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.[177Lu]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 [177Lu]Lu-PSMA-617 in patients with metastatic castration-resistant prostate cancer who received previous androgen receptor pathway inhibitor and taxane treatment.Advanced Accelerator Applications (Novartis). 000276405 536__ $$0G:(DE-HGF)POF4-899$$a899 - ohne Topic (POF4-899)$$cPOF4-899$$fPOF IV$$x0 000276405 588__ $$aDataset connected to CrossRef, PubMed, , Journals: inrepo02.dkfz.de 000276405 650_7 $$2NLM Chemicals$$aPSMA-617 000276405 650_7 $$2NLM Chemicals$$aReceptors, Androgen 000276405 650_7 $$2NLM Chemicals$$aAndrogen Receptor Antagonists 000276405 650_7 $$01605-68-1$$2NLM Chemicals$$ataxane 000276405 650_7 $$2NLM Chemicals$$aTaxoids 000276405 650_2 $$2MeSH$$aMale 000276405 650_2 $$2MeSH$$aHumans 000276405 650_2 $$2MeSH$$aAged 000276405 650_2 $$2MeSH$$aQuality of Life 000276405 650_2 $$2MeSH$$aProstatic Neoplasms, Castration-Resistant: drug therapy 000276405 650_2 $$2MeSH$$aReceptors, Androgen 000276405 650_2 $$2MeSH$$aStandard of Care 000276405 650_2 $$2MeSH$$aAndrogen Receptor Antagonists: adverse effects 000276405 650_2 $$2MeSH$$aPain: chemically induced 000276405 650_2 $$2MeSH$$aTaxoids 000276405 650_2 $$2MeSH$$aAntineoplastic Combined Chemotherapy Protocols: adverse effects 000276405 7001_ $$0P:(DE-HGF)0$$aHerrmann, Ken$$b1 000276405 7001_ $$aKrause, Bernd J$$b2 000276405 7001_ $$aRahbar, Kambiz$$b3 000276405 7001_ $$aChi, Kim N$$b4 000276405 7001_ $$aMorris, Michael J$$b5 000276405 7001_ $$aSartor, Oliver$$b6 000276405 7001_ $$aTagawa, Scott T$$b7 000276405 7001_ $$aKendi, Ayse T$$b8 000276405 7001_ $$aVogelzang, Nicholas$$b9 000276405 7001_ $$aCalais, Jeremie$$b10 000276405 7001_ $$aNagarajah, James$$b11 000276405 7001_ $$aWei, Xiao X$$b12 000276405 7001_ $$aKoshkin, Vadim S$$b13 000276405 7001_ $$aBeauregard, Jean-Mathieu$$b14 000276405 7001_ $$aChang, Brian$$b15 000276405 7001_ $$aGhouse, Ray$$b16 000276405 7001_ $$aDeSilvio, Michelle$$b17 000276405 7001_ $$aMessmann, Richard A$$b18 000276405 7001_ $$ade Bono, Johann$$b19 000276405 773__ $$0PERI:(DE-600)2035574-9$$a10.1016/S1470-2045(23)00158-4$$gVol. 24, no. 6, p. 597 - 610$$n6$$p597 - 610$$tThe lancet <London> / Oncology$$v24$$x1470-2045$$y2023 000276405 909CO $$ooai:inrepo02.dkfz.de:276405$$pVDB 000276405 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-HGF)0$$aDeutsches Krebsforschungszentrum$$b1$$kDKFZ 000276405 9131_ $$0G:(DE-HGF)POF4-899$$1G:(DE-HGF)POF4-890$$2G:(DE-HGF)POF4-800$$3G:(DE-HGF)POF4$$4G:(DE-HGF)POF$$aDE-HGF$$bProgrammungebundene Forschung$$lohne Programm$$vohne Topic$$x0 000276405 9141_ $$y2023 000276405 915__ $$0StatID:(DE-HGF)0113$$2StatID$$aWoS$$bScience Citation Index Expanded$$d2022-11-29 000276405 915__ $$0StatID:(DE-HGF)0160$$2StatID$$aDBCoverage$$bEssential Science Indicators$$d2022-11-29 000276405 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS$$d2023-08-25 000276405 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline$$d2023-08-25 000276405 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List$$d2023-08-25 000276405 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection$$d2023-08-25 000276405 915__ $$0StatID:(DE-HGF)1110$$2StatID$$aDBCoverage$$bCurrent Contents - Clinical Medicine$$d2023-08-25 000276405 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bLANCET ONCOL : 2022$$d2023-08-25 000276405 915__ $$0StatID:(DE-HGF)0600$$2StatID$$aDBCoverage$$bEbsco Academic Search$$d2023-08-25 000276405 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bASC$$d2023-08-25 000276405 915__ $$0StatID:(DE-HGF)9950$$2StatID$$aIF >= 50$$bLANCET ONCOL : 2022$$d2023-08-25 000276405 9201_ $$0I:(DE-He78)ED01-20160331$$kED01$$lDKTK ED ES zentral$$x0 000276405 980__ $$ajournal 000276405 980__ $$aVDB 000276405 980__ $$aI:(DE-He78)ED01-20160331 000276405 980__ $$aUNRESTRICTED