Your browser doesn't support javascript.
loading
[177Lu]Lu-PSMA-617 versus cabazitaxel in patients with metastatic castration-resistant prostate cancer (TheraP): a randomised, open-label, phase 2 trial.
Hofman, Michael S; Emmett, Louise; Sandhu, Shahneen; Iravani, Amir; Joshua, Anthony M; Goh, Jeffrey C; Pattison, David A; Tan, Thean Hsiang; Kirkwood, Ian D; Ng, Siobhan; Francis, Roslyn J; Gedye, Craig; Rutherford, Natalie K; Weickhardt, Andrew; Scott, Andrew M; Lee, Sze-Ting; Kwan, Edmond M; Azad, Arun A; Ramdave, Shakher; Redfern, Andrew D; Macdonald, William; Guminski, Alex; Hsiao, Edward; Chua, Wei; Lin, Peter; Zhang, Alison Y; McJannett, Margaret M; Stockler, Martin R; Violet, John A; Williams, Scott G; Martin, Andrew J; Davis, Ian D.
  • Hofman MS; Prostate Cancer Theranostics and Imaging Centre of Excellence, Molecular Imaging and Therapeutic Nuclear Medicine, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia. Electronic address: michael.hof
  • Emmett L; Department of Theranostics and Nuclear Medicine, St Vincent's Hospital, Sydney, NSW, Australia; Faculty of Medicine, UNSW Sydney, Sydney, NSW, Australia.
  • Sandhu S; Prostate Cancer Theranostics and Imaging Centre of Excellence, Molecular Imaging and Therapeutic Nuclear Medicine, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia.
  • Iravani A; Prostate Cancer Theranostics and Imaging Centre of Excellence, Molecular Imaging and Therapeutic Nuclear Medicine, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia; Mallinckrodt Institute of Radiology, Washington University, St Louis, MO, USA.
  • Joshua AM; Department of Medical Oncology, Kinghorn Cancer Centre, St Vincent's Hospital, Sydney, NSW, Australia.
  • Goh JC; Medical Oncology, Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia.
  • Pattison DA; Department of Nuclear Medicine & Specialised PET Services, Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia; School of Medicine, University of Queensland, St Lucia, Brisbane, QLD, Australia.
  • Tan TH; Department of Oncology, Royal Adelaide Hospital, Adelaide, SA, Australia; Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, SA Australia.
  • Kirkwood ID; Department of Oncology, Royal Adelaide Hospital, Adelaide, SA, Australia; Department of Nuclear Medicine and PET, Royal Adelaide Hospital, Adelaide, SA, Australia; Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, SA Australia.
  • Ng S; Department of Oncology, Sir Charles Gairdner Hospital, Perth, WA, Australia; Medical School, University of Western Australia, Perth, WA, Australia.
  • Francis RJ; Department of Nuclear Medicine, Sir Charles Gairdner Hospital, Perth, WA, Australia; Medical School, University of Western Australia, Perth, WA, Australia.
  • Gedye C; Department of Medical Oncology, Calvary Mater Newcastle, Waratah, NSW, Australia; School of Medicine and Public Health, University of Newcastle, Newcastle, NSW, Australia.
  • Rutherford NK; Department of Nuclear Medicine, Hunter New England Health, Newcastle, NSW, Australia; School of Medicine and Public Health, University of Newcastle, Newcastle, NSW, Australia.
  • Weickhardt A; Olivia Newton-John Cancer and Wellness Centre, Austin Health, Melbourne, VIC, Australia; School of Cancer Medicine, La Trobe University, Melbourne, VIC, Australia.
  • Scott AM; Department of Medicine, University of Melbourne, 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,
  • Lee ST; Department of Medicine, University of Melbourne, 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,
  • Kwan EM; Department of Medical Oncology, Monash Health, Melbourne, VIC, Australia.
  • Azad AA; Prostate Cancer Theranostics and Imaging Centre of Excellence, Molecular Imaging and Therapeutic Nuclear Medicine, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia.
  • Ramdave S; Monash Health Imaging, Monash Health, Melbourne, VIC, Australia.
  • Redfern AD; Medical School, University of Western Australia, Perth, WA, Australia; Department of Medical Oncology, Fiona Stanley Hospital, Perth, WA, Australia.
  • Macdonald W; Department of Nuclear Medicine, Fiona Stanley Hospital, Perth, WA, Australia.
  • Guminski A; Department of Medical Oncology, Royal North Shore Hospital, Sydney, NSW, Australia; Northern Clinical School, University of Sydney, Sydney, NSW, Australia.
  • Hsiao E; Department of Nuclear Medicine and PET, Royal North Shore Hospital, Sydney, NSW, Australia.
  • Chua W; Department of Medical Oncology, Liverpool Hospital, Sydney, NSW, Australia.
  • Lin P; Faculty of Medicine, UNSW Sydney, Sydney, NSW, Australia; Department of Nuclear Medicine and PET, Liverpool Hospital, Sydney, NSW, Australia.
  • Zhang AY; NHMRC Clinical Trials Centre, University of Sydney, Sydney, NSW, Australia; Department of Medical Oncology, Macquarie University Hospital, Sydney, NSW, Australia; Department of Medical Oncology, Chris O'Brien Lifehouse, Sydney, NSW, Australia.
  • McJannett MM; Australian and New Zealand Urogenital and Prostate Cancer Trials Group, Sydney, NSW, Australia.
  • Stockler MR; NHMRC Clinical Trials Centre, University of Sydney, Sydney, NSW, Australia; Department of Medical Oncology, Chris O'Brien Lifehouse, Sydney, NSW, Australia.
  • Violet JA; Prostate Cancer Theranostics and Imaging Centre of Excellence, Molecular Imaging and Therapeutic Nuclear Medicine, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia.
  • Williams SG; Prostate Cancer Theranostics and Imaging Centre of Excellence, Molecular Imaging and Therapeutic Nuclear Medicine, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia.
  • Martin AJ; NHMRC Clinical Trials Centre, University of Sydney, Sydney, NSW, Australia.
  • Davis ID; Eastern Health Clinical School, Monash University, Melbourne, VIC, Australia; Eastern Health, Melbourne, VIC, Australia.
Lancet ; 397(10276): 797-804, 2021 02 27.
Article en En | MEDLINE | ID: mdl-33581798
BACKGROUND: Lutetium-177 [177Lu]Lu-PSMA-617 is a radiolabelled small molecule that delivers ß radiation to cells expressing prostate-specific membrane antigen (PSMA), with activity and safety in patients with metastatic castration-resistant prostate cancer. We aimed to compare [177Lu]Lu-PSMA-617 with cabazitaxel in patients with metastatic castration-resistant prostate cancer. METHODS: We did this multicentre, unblinded, randomised phase 2 trial at 11 centres in Australia. We recruited men with metastatic castration-resistant prostate cancer for whom cabazitaxel was considered the next appropriate standard treatment. Participants were required to have adequate renal, haematological, and liver function, and an Eastern Cooperative Oncology Group performance status of 0-2. Previous treatment with androgen receptor-directed therapy was allowed. Men underwent gallium-68 [68Ga]Ga-PSMA-11 and 2-flourine-18[18F]fluoro-2-deoxy-D-glucose (FDG) PET-CT scans. PET eligibility criteria for the trial were PSMA-positive disease, and no sites of metastatic disease with discordant FDG-positive and PSMA-negative findings. Men were randomly assigned (1:1) to [177Lu]Lu-PSMA-617 (6·0-8·5 GBq intravenously every 6 weeks for up to six cycles) or cabazitaxel (20 mg/m2 intravenously every 3 weeks for up to ten cycles). The primary endpoint was prostate-specific antigen (PSA) response defined by a reduction of at least 50% from baseline. This trial is registered with ClinicalTrials.gov, NCT03392428. FINDINGS: Between Feb 6, 2018, and Sept 3, 2019, we screened 291 men, of whom 200 were eligible on PET imaging. Study treatment was received by 98 (99%) of 99 men randomly assigned to [177Lu]Lu-PSMA-617 versus 85 (84%) of 101 randomly assigned to cabazitaxel. PSA responses were more frequent among men in the [177Lu]Lu-PSMA-617 group than in the cabazitaxel group (65 vs 37 PSA responses; 66% vs 37% by intention to treat; difference 29% (95% CI 16-42; p<0·0001; and 66% vs 44% by treatment received; difference 23% [9-37]; p=0·0016). Grade 3-4 adverse events occurred in 32 (33%) of 98 men in the [177Lu]Lu-PSMA-617 group versus 45 (53%) of 85 men in the cabazitaxel group. No deaths were attributed to [177Lu]Lu-PSMA-617. INTERPRETATION: [177Lu]Lu-PSMA-617 compared with cabazitaxel in men with metastatic castration-resistant prostate cancer led to a higher PSA response and fewer grade 3 or 4 adverse events. [177Lu]Lu-PSMA-617 is a new effective class of therapy and a potential alternative to cabazitaxel. FUNDING: Prostate Cancer Foundation of Australia, Endocyte (a Novartis company), Australian Nuclear Science and Technology Organization, Movember, The Distinguished Gentleman's Ride, It's a Bloke Thing, and CAN4CANCER.
Asunto(s)
Texto completo
Imprimir
XML
PubMed Links
Search on Google

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Radioisótopos / Antígeno Prostático Específico / Taxoides / Dipéptidos / Neoplasias de la Próstata Resistentes a la Castración / Compuestos Heterocíclicos con 1 Anillo / Lutecio Tipo de estudio: Clinical_trials Límite: Aged / Humans / Male Idioma: En Año: 2021 Tipo del documento: Article
Texto completo
Imprimir
XML
PubMed Links
Search on Google

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Radioisótopos / Antígeno Prostático Específico / Taxoides / Dipéptidos / Neoplasias de la Próstata Resistentes a la Castración / Compuestos Heterocíclicos con 1 Anillo / Lutecio Tipo de estudio: Clinical_trials Límite: Aged / Humans / Male Idioma: En Año: 2021 Tipo del documento: Article