Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/27752
Title: [177Lu]Lu-PSMA-617 versus cabazitaxel in patients with metastatic castration-resistant prostate cancer (TheraP): a randomised, open-label, phase 2 trial.
Austin Authors: 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 J ;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
Affiliation: Department of Nuclear Medicine and PET, Liverpool Hospital, Sydney, NSW, Australia
Eastern Health, Melbourne, VIC, Australia
Olivia Newton-John Cancer Wellness and Research Centre
Department of Medical Oncology, Kinghorn Cancer Centre, St Vincent's Hospital, Sydney, NSW, Australia
Medical Oncology, Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia
Department of Oncology, Royal Adelaide Hospital, Adelaide, SA, Australia
Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, SA Australia
Department of Nuclear Medicine and PET, Royal Adelaide Hospital, Adelaide, SA, Australia
Department of Oncology, Sir Charles Gairdner Hospital, Perth, WA, Australia
Medical School, University of Western Australia, Perth, WA, Australia
Department of Nuclear Medicine, Sir Charles Gairdner Hospital, Perth, WA, Australia
Department of Medical Oncology, Calvary Mater Newcastle, Waratah, NSW, Australia
School of Medicine and Public Health, University of Newcastle, Newcastle, NSW, Australia
Department of Nuclear Medicine, Hunter New England Health, Newcastle, NSW, Australia
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
Mallinckrodt Institute of Radiology, Washington University, St Louis, MO, USA
Department of Theranostics and Nuclear Medicine, St Vincent's Hospital, Sydney, NSW, Australia
Faculty of Medicine, UNSW Sydney, Sydney, NSW, Australia
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
Department of Medicine, University of Melbourne, Melbourne, VIC, Australia
Molecular Imaging and Therapy
School of Cancer Medicine, La Trobe University, Melbourne, VIC, Australia
Olivia Newton-John Cancer Research Institute
Department of Medical Oncology, Fiona Stanley Hospital, Perth, WA, Australia
Department of Medical Oncology, Monash Health, Melbourne, VIC, Australia
Department of Medical Oncology, Royal North Shore Hospital, Sydney, NSW, Australia
Northern Clinical School, University of Sydney, Sydney, NSW, Australia
Monash Health Imaging, Monash Health, Melbourne, VIC, Australia
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
Department of Nuclear Medicine, Fiona Stanley Hospital, Perth, WA, Australia
Department of Nuclear Medicine and PET, Royal North Shore Hospital, Sydney, NSW, Australia
Department of Medical Oncology, Liverpool Hospital, Sydney, NSW, Australia
Australian and New Zealand Urogenital and Prostate Cancer Trials Group, Sydney, NSW, Australia
Eastern Health Clinical School, Monash University, Melbourne, VIC, Australia
Issue Date: 27-Feb-2021
Date: 2021-02-11
Publication information: Lancet 2021; 397(10276): 797-804
Abstract: Lutetium-177 [177Lu]Lu-PSMA-617 is a radiolabelled small molecule that delivers β 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. 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. 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. [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. 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.
URI: https://ahro.austin.org.au/austinjspui/handle/1/27752
DOI: 10.1016/S0140-6736(21)00237-3
Journal: Lancet
PubMed URL: 33581798
Type: Journal Article
Appears in Collections:Journal articles

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