[177Lu]Lu-PSMA-617 versus cabazitaxel in patients with metastatic castration-resistant prostate cancer (TheraP): a randomised, open-label, phase 2 trial
[177Lu]Lu-PSMA-617 versus cabazitaxel in patients with metastatic castration-resistant prostate cancer (TheraP): a randomised, open-label, phase 2 trial
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DOI：
10.1016/s0140-6736(21)00237-3
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发表时间：
2021-02-25
期刊：
影响因子：
168.9
通讯作者：
Davis, Ian D.
中科院分区：
文献类型：
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作者：
Hofman, Michael S.;Emmett, Louise;Davis, Ian D.
Lutetium-177 [Lu-177] lutetium -PSMA-617是一种放射性标记的小分子，可向表达前列腺特异性膜抗原（PSMA）的细胞传递β辐射，在转移性去势抵抗性前列腺癌患者中具有活性和安全性。我们的目的是比较[u-177] u- psma -617与卡巴他赛在转移性去势抵抗性前列腺癌患者中的疗效。方法：我们在澳大利亚的11个中心进行了这项多中心、非盲、随机2期试验。我们招募了患有转移性去势抵抗性前列腺癌的男性，卡巴他赛被认为是下一个合适的标准治疗。参与者被要求有足够的肾脏、血液学和肝功能，并且东部肿瘤合作组的表现状态为0-2。以前接受过雄激素受体定向治疗。男性接受镓-68 [Ga-68]Ga-PSMA-11和2-氟-18[F-18]氟-2-脱氧-d -葡萄糖（FDG） PET-CT扫描。该试验的PET资格标准是psma阳性疾病，无fdg阳性和psma阴性结果不一致的转移性疾病部位。男性随机分配（1:1）至[Lu-177] Lu-PSMA-617 （6.0-8-5 GBq，每6周静脉注射，最多6个周期）或卡巴他赛（20mg /m(2)，每3周静脉注射，最多10个周期）。主要终点是前列腺特异性抗原（PSA）反应，定义为比基线减少至少50%。该试验已在ClinicalTrials.gov注册，注册号为NCT03392428。在2018年2月6日至2019年9月3日期间，我们筛查了291名男性，其中200名符合PET成像条件。99名男性中有98名（99%）接受了研究治疗，随机分配给[Lu-177]Lu-PSMA-617，而101名男性中有85名（84%）接受了卡巴他赛。[Lu-177]Lu-PSMA-617组男性的PSA反应比卡巴他赛组更频繁(65 vs 37 PSA反应；66% vs 37%的意向治疗；差异29% (95% CI 16-42; p
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