[177Lu]Lu-PSMA-617 versus cabazitaxel in patients with metastatic castration-resistant prostate cancer (TheraP): a randomised, open-label, phase 2 trial

被引：670

作者：

Hofman, Michael S. ^{[1
,2
]}

Emmett, Louise ^{[4
,6
]}

Sandhu, Shahneen ^{[1
,2
]}

Iravani, Amir ^{[1
,7
]}

Joshua, Anthony M. ^{[5
]}

Goh, Jeffrey C. ^{[9
]}

Pattison, David A. ^{[8
,10
]}

Tan, Thean Hsiang ^{[11
,13
]}

Kirkwood, Ian D. ^{[11
,12
,13
]}

Ng, Siobhan ^{[14
,16
]}

Francis, Roslyn J. ^{[15
,16
]}

Gedye, Craig ^{[17
,19
]}

Rutherford, Natalie K. ^{[18
,19
]}

Weickhardt, Andrew ^{[20
,22
]}

Scott, Andrew M. ^{[3
,21
,22
,23
]}

Lee, Sze-Ting ^{[3
,21
,22
,23
]}

Kwan, Edmond M. ^{[24
]}

Azad, Arun A. ^{[1
,2
]}

Ramdave, Shakher ^{[25
]}

Redfern, Andrew D. ^{[16
,26
]}

Macdonald, William ^{[27
]}

Guminski, Alex ^{[28
,30
]}

Hsiao, Edward ^{[29
]}

Chua, Wei ^{[31
]}

Lin, Peter ^{[6
,32
]}

Zhang, Alison Y. ^{[30
,34
,35
]}

McJannett, Margaret M. ^{[33
]}

Stockler, Martin R. ^{[30
,35
]}

Violet, John A. ^{[1
,2
]}

Williams, Scott G. ^{[1
,2
]}

Martin, Andrew J. ^{[30
]}

Davis, Ian D. ^{[36
,37
]}

机构：

[1] Peter MacCallum Canc Ctr, Prostate Canc Theranost & Imaging Ctr Excellence, Mol Imaging & Therapeut Nucl Med, Melbourne, Vic, Australia

[2] Univ Melbourne, Sir Peter MacCallum Dept Oncol, Melbourne, Vic, Australia

[3] Univ Melbourne, Dept Med, Melbourne, Vic, Australia

[4] St Vincents Hosp, Dept Theranost & Nucl Med, Sydney, NSW, Australia

[5] St Vincents Hosp, Dept Med Oncol, Kinghorn Canc Ctr, Sydney, NSW, Australia

[6] UNSW Sydney, Fac Med, Sydney, NSW, Australia

[7] Washington Univ, Mallinckrodt Inst Radiol, St Louis, MO 63110 USA

[8] Royal Brisbane & Womens Hosp, Dept Nucl Med & Specialised PET Serv, Brisbane, Qld, Australia

[9] Royal Brisbane & Womens Hosp, Dept Med Oncol, Brisbane, Qld, Australia

[10] Univ Queensland, Sch Med, Brisbane, Qld, Australia

[11] Royal Adelaide Hosp, Dept Oncol, Adelaide, SA, Australia

[12] Royal Adelaide Hosp, Dept Nucl Med & PET, Adelaide, SA, Australia

[13] Univ Adelaide, Fac Hlth & Med Sci, Adelaide, SA, Australia

[14] Sir Charles Gairdner Hosp, Dept Oncol, Perth, WA, Australia

[15] Sir Charles Gairdner Hosp, Dept Nucl Med, Perth, WA, Australia

[16] Univ Western Australia, Sch Med, Perth, WA, Australia

[17] Calvary Mater Newcastle, Dept Med Oncol, Waratah, NSW, Australia

[18] Hunter New England Hlth, Dept Nucl Med, Newcastle, NSW, Australia

[19] Univ Newcastle, Sch Med & Publ Hlth, Newcastle, NSW, Australia

[20] Austin Hlth, Olivia Newton John Canc & Wellness Ctr, Melbourne, Vic, Australia

[21] Austin Hlth, Dept Mol Imaging & Therapy, Melbourne, Vic, Australia

[22] La Trobe Univ, Sch Canc Med, Melbourne, Vic, Australia

[23] Olivia Newton John Canc Res Inst, Melbourne, Vic, Australia

[24] Monash Hlth, Dept Med Oncol, Melbourne, Vic, Australia

[25] Monash Hlth, Monash Hlth Imaging, Melbourne, Vic, Australia

[26] Fiona Stanley Hosp, Dept Med Oncol, Perth, WA, Australia

[27] Fiona Stanley Hosp, Dept Nucl Med, Perth, WA, Australia

[28] Royal North Shore Hosp, Dept Med Oncol, Sydney, NSW, Australia

[29] Royal North Shore Hosp, Dept Nucl Med & PET, Sydney, NSW, Australia

[30] Univ Sydney, NHMRC Clin Trials Ctr, Northern Clin Sch, Sydney, NSW, Australia

[31] Liverpool Hosp, Dept Med Oncol, Sydney, NSW, Australia

[32] Liverpool Hosp, Dept Nucl Med & PET, Sydney, NSW, Australia

[33] Australian & New Zealand Urogenital & Prostate Ca, Sydney, NSW, Australia

[34] Macquarie Univ Hosp, Dept Med Oncol, Sydney, NSW, Australia

[35] Chris OBrien Lifehouse, Dept Med Oncol, Sydney, NSW, Australia

[36] Monash Univ, Eastern Hlth Clin Sch, Melbourne, Vic, Australia

[37] Eastern Hlth, Melbourne, Vic, Australia

来源：

LANCET | 2021年 / 397卷 / 10276期

关键词：

D O I：

10.1016/S0140-6736(21)00237-3

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Background Lutetium-177 [Lu-177]Lu-PSMA-617 is a radiolabelled small molecule that delivers beta 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 [Lu-177]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 [Ga-68]Ga-PSMA-11 and 2-flourine-18[F-18]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 [Lu-177] Lu-PSMA-617 (6.0-8-5 GBq intravenously every 6 weeks for up to six cycles) or cabazitaxel (20 mg/m(2) 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 [Lu-177]Lu-PSMA-617 versus 85 (84%) of 101 randomly assigned to cabazitaxel. PSA responses were more frequent among men in the [Lu-177]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 [Lu-177]Lu-PSMA-617 group versus 45 (53%) of 85 men in the cabazitaxel group. No deaths were attributed to [Lu-177]Lu-PSMA-617. Interpretation [Lu-177]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. [Lu-177]Lu-PSMA-617 is a new effective class of therapy and a potential alternative to cabazitaxel. Copyright (C) 2021 Elsevier Ltd. All rights reserved.

引用

页码：797 / 804

页数：8

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