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https://swslhd.intersearch.com.au/swslhdjspui/handle/1/12685Full metadata record
| DC Field | Value | Language |
|---|---|---|
| dc.contributor.author | Emmett, L. | - |
| dc.contributor.author | Subramaniam, S. | - |
| dc.contributor.author | Crumbaker, M. | - |
| dc.contributor.author | Nguyen, A. | - |
| dc.contributor.author | Joshua, A. M. | - |
| dc.contributor.author | Weickhardt, A. | - |
| dc.contributor.author | Lee, S. T. | - |
| dc.contributor.author | Ng, S. | - |
| dc.contributor.author | Francis, R. J. | - |
| dc.contributor.author | Goh, J. C. | - |
| dc.contributor.author | Pattison, D. A. | - |
| dc.contributor.author | Tan, T. H. | - |
| dc.contributor.author | Kirkwood, I. D. | - |
| dc.contributor.author | Gedye, C. | - |
| dc.contributor.author | Rutherford, N. K. | - |
| dc.contributor.author | Sandhu, S. | - |
| dc.contributor.author | Kumar, A. R. | - |
| dc.contributor.author | Pook, D. | - |
| dc.contributor.author | Ramdave, S. | - |
| dc.contributor.author | Nadebaum, D. P. | - |
| dc.contributor.author | Voskoboynik, M. | - |
| dc.contributor.author | Redfern, A. D. | - |
| dc.contributor.author | Macdonald, W. | - |
| dc.contributor.author | Krieger, L. | - |
| dc.contributor.author | Schembri, G. | - |
| dc.contributor.author | Chua, W. | - |
| dc.contributor.author | Lin, P. | - |
| dc.contributor.author | Horvath, L. | - |
| dc.contributor.author | Bastick, P. | - |
| dc.contributor.author | Butler, P. | - |
| dc.contributor.author | Zhang, A. Y. | - |
| dc.contributor.author | Yip, S. | - |
| dc.contributor.author | Thomas, H. | - |
| dc.contributor.author | Langford, A. | - |
| dc.contributor.author | Hofman, M. S. | - |
| dc.contributor.author | McJannett, M. | - |
| dc.contributor.author | Martin, A. J. | - |
| dc.contributor.author | Stockler, M. R. | - |
| dc.contributor.author | Davis, I. D. | - |
| dc.date.accessioned | 2024-06-03T03:25:27Z | - |
| dc.date.available | 2024-06-03T03:25:27Z | - |
| dc.date.issued | 2024 | - |
| dc.identifier.issn | 14702045 (ISSN) | - |
| dc.identifier.uri | https://swslhd.intersearch.com.au/swslhdjspui/handle/1/12685 | - |
| dc.description.abstract | Background: Enzalutamide and lutetium-177 [177Lu]Lu-prostate-specific membrane antigen (PSMA)-617 both improve overall survival in patients with metastatic castration-resistant prostate cancer. Androgen and PSMA receptors have a close intracellular relationship, with data suggesting complementary benefit if targeted concurrently. In this study, we assessed the activity and safety of enzalutamide plus adaptive-dosed [177Lu]Lu-PSMA-617 versus enzalutamide alone as first-line treatment for metastatic castration-resistant prostate cancer. Methods: ENZA-p was an open-label, randomised, controlled phase 2 trial done at 15 hospitals in Australia. Participants were men aged 18 years or older with metastatic castration-resistant prostate cancer not previously treated with docetaxel or androgen receptor pathway inhibitors for metastatic castration-resistant prostate cancer, gallium-68 [68Ga]Ga-PSMA-PET-CT (PSMA-PET-CT) positive disease, Eastern Cooperative Oncology Group performance status of 0-2, and at least two risk factors for early progression on enzalutamide. Participants were randomly assigned (1:1) by a centralised, web-based system using minimisation with a random component to stratify for study site, disease burden, use of early docetaxel, and previous treatment with abiraterone acetate. Patients were either given oral enzalutamide 160 mg daily alone or with adaptive-dosed (two or four doses) intravenous 7·5 GBq [177Lu]Lu-PSMA-617 every 6-8 weeks dependent on an interim PSMA-PET-CT (week 12). The primary endpoint was prostate-specific antigen (PSA) progression-free survival, defined as the interval from the date of randomisation to the date of first evidence of PSA progression, commencement of non-protocol anticancer therapy, or death. The analysis was done in the intention-to-treat population, using stratified Cox proportional hazards regression. This trial is registered with ClinicalTrials.gov, NCT04419402, and participant follow-up is ongoing. Findings: 162 participants were randomly assigned between Aug 17, 2020, and July 26, 2022. 83 men were assigned to the enzalutamide plus [177Lu]Lu-PSMA-617 group, and 79 were assigned to the enzalutamide group. Median follow-up in this interim analysis was 20 months (IQR 18-21), with 32 (39%) of 83 patients in the enzalutamide plus [177Lu]Lu-PSMA-617 group and 16 (20%) of 79 patients in the enzalutamide group remaining on treatment at the data cutoff date. Median age was 71 years (IQR 64-76). Median PSA progression-free survival was 13·0 months (95% CI 11·0-17·0) in the enzalutamide plus [177Lu]Lu-PSMA-617 group and 7·8 months (95% CI 4·3-11·0) in the enzalutamide group (hazard ratio 0·43, 95% CI 0·29-0·63, p<0·0001). The most common adverse events (all grades) were fatigue (61 [75%] of 81 patients), nausea (38 [47%]), and dry mouth (32 [40%]) in the enzalutamide plus [177Lu]Lu-PSMA-617 group and fatigue (55 [70%] of 79), nausea (21 [27%]), and constipation (18 [23%]) in the enzalutamide group. Grade 3-5 adverse events occurred in 32 (40%) of 81 patients in the enzalutamide plus [177Lu]Lu-PSMA-617 group and 32 (41%) of 79 patients in the enzalutamide group. Grade 3 events that occurred only in the enzalutamide plus [177Lu]Lu-PSMA-617 group included anaemia (three [4%] of 81 participants) and decreased platelet count (one [1%] participant). No grade 4 or 5 events were attributed to treatment on central review in either group. Interpretation: The addition of [177Lu]Lu-PSMA-617 to enzalutamide improved PSA progression-free survival providing evidence of enhanced anticancer activity in patients with metastatic castration-resistant prostate cancer with risk factors for early progression on enzalutamide and warrants further evaluation of the combination more broadly in metastatic prostate cancer. Funding: Prostate Cancer Research Alliance (Movember and Australian Federal Government), St Vincent's Clinic Foundation, GenesisCare, Roy Morgan Research, and Endocyte (a Novartis company). © 2024 Elsevier Ltd | - |
| dc.publisher | Elsevier Ltd | - |
| dc.subject | Aged Aged, 80 and over Antineoplastic Combined Chemotherapy Protocols Benzamides Dipeptides Heterocyclic Compounds, 1-Ring Humans Lutetium Male Middle Aged Nitriles Phenylthiohydantoin Progression-Free Survival Prostate-Specific Antigen Prostatic Neoplasms, Castration-Resistant Radioisotopes Radiopharmaceuticals abiraterone acetate androgen receptor docetaxel enzalutamide fluorodeoxyglucose f 18 gallium 68 lactate dehydrogenase lutetium 177 prostate specific membrane antigen antineoplastic agent benzamide derivative dipeptide Lutetium-177 nitrile prostate specific antigen PSMA-617 radioisotope radiopharmaceutical agent single heterocyclic rings anemia anorexia arthralgia Article cardiovascular disease constipation controlled study dry eye dysphagia fatigue first-line treatment follow up human major clinical study metastatic castration resistant prostate cancer multicenter study nausea overall survival phase 2 clinical trial positron emission tomography-computed tomography progression free survival randomized controlled trial risk factor single photon emission computed tomography thrombocytopenia xerostomia blood castration resistant prostate cancer clinical trial mortality pathology very elderly | - |
| dc.title | [177Lu]Lu-PSMA-617 plus enzalutamide in patients with metastatic castration-resistant prostate cancer (ENZA-p): an open-label, multicentre, randomised, phase 2 trial | - |
| dc.type | Journal Article | - |
| dc.contributor.swslhdauthor | Chua, Wei | - |
| dc.contributor.swslhdauthor | Lin, Peter | - |
| dc.contributor.swslhdauthor | Subramaniam, Shalini | - |
| dc.description.affiliates | Department of Theranostics and Nuclear Medicine, St Vincent's Hospital, Sydney, NSW, Australia Department of Medical Oncology, Kinghorn Cancer Centre, St Vincent's Hospital, Sydney, NSW, Australia St Vincent's Clinical School, University of New South Wales, Sydney, NSW, Australia South Western Sydney Clinical School, University of New South Wales, Sydney, NSW, Australia Garvan Institute of Medical Research, Sydney, NSW, Australia NHMRC Clinical Trials Centre, University of Sydney, Sydney, NSW, Australia Department of Medical Oncology, Bankstown-Lidcombe Hospital, Sydney, NSW, Australia Macquarie University Hospital, Sydney, NSW, Australia Olivia Newton-John Cancer and Wellness Centre, Austin Health, Melbourne, VIC, Australia Department of Molecular Imaging and Therapy, Austin Health, Melbourne, VIC, Australia School of Cancer Medicine, La Trobe University, Melbourne, VIC, Australia Olivia Newton-John Cancer Research Institute, Melbourne, VIC, Australia Department of Medicine and Department of Surgery, University of Melbourne, Melbourne, VIC, Australia Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia Department of Oncology, Sir Charles Gairdner Hospital, Perth, WA, Australia Department of Nuclear Medicine, Sir Charles Gairdner Hospital, Perth, WA, Australia Department of Oncology, University of Western Australia, Perth, WA, Australia Medical School, University of Western Australia, Perth, WA, Australia Department of Medical Oncology, Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia Department of Nuclear Medicine and Specialised PET Services, Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia Queensland University of Technology, Brisbane, QLD, Australia School of Medicine, University of Queensland, Brisbane, QLD, Australia Centre for Clinical Research, University of Queensland, Brisbane, QLD, Australia Department of Medical Oncology, Royal Adelaide Hospital, Adelaide, SA, Australia Nuclear Medicine, PET and Bone Densitometry, Royal Adelaide Hospital, Adelaide, SA, Australia Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, SA, Australia Department of Medical Oncology, Calvary Mater Newcastle, Waratah, NSW, Australia Department of Nuclear Medicine, Hunter New England Health, Newcastle, NSW, Australia Prostate Cancer Theranostics and Imaging Centre of Excellence (ProsTIC), Molecular Imaging and Therapeutic Nuclear Medicine, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia Department of Oncology, Monash Health, Melbourne, VIC, Australia Monash Health Imaging, Monash Health, Melbourne, VIC, Australia Department of Oncology, Alfred Health, Melbourne, VIC, Australia Central Clinical School, Monash University, Melbourne, VIC, Australia Department of Medical Oncology, Fiona Stanley Hospital, Perth, WA, Australia Department of Nuclear Medicine, Fiona Stanley Hospital, Perth, WA, Australia Genesis Care North Shore, Sydney, NSW, Australia Nuclear Medicine, Royal North Shore Hospital, Sydney, NSW, Australia Department of Medical Oncology, Liverpool Hospital, Sydney, NSW, Australia Department of Nuclear Medicine and PET, Liverpool Hospital, Sydney, NSW, Australia Western Sydney University, Sydney, NSW, Australia Department of Medical Oncology, Chris O'Brien Lifehouse, Sydney, NSW, Australia Department of Medical Oncology, St George Hospital, Sydney, NSW, Australia Department of Nuclear Medicine, St George Hospital, Sydney, NSW, Australia Australian and New Zealand Urogenital and Prostate Cancer Trials Group, Sydney, NSW, Australia Monash University Eastern Health Clinical School, Melbourne, VIC, Australia Eastern Health, Melbourne, VIC, Australia | - |
| dc.identifier.doi | 10.1016/S1470-2045(24)00135-9 | - |
| dc.identifier.department | Liverpool Hospital, Department of Medical Oncology | - |
| dc.identifier.department | Liverpool Hospital, Department of Nuclear Medicine and PET | - |
| dc.identifier.department | Bankstown-Lidcombe Hospital, Department of Medical Oncology | - |
| dc.type.studyortrial | Article | - |
| dc.identifier.journaltitle | The Lancet Oncology | - |
| Appears in Collections: | Bankstown-Lidcombe Hospital Liverpool Hospital | |
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