澳大利亚彼得·麦卡勒姆癌症中心Michael S Hofman团队比较了[177Lu]Lu-PSMA-617与卡巴他赛治疗转移性去势性前列腺癌的疗效。2021年2月27日，该研究发表在《柳叶刀》杂志上。

镥-177[177Lu] Lu-PSMA-617是一种放射性标记的小分子，可将β辐射传递给表达前列腺特异性膜抗原（PSMA）的细胞，在转移性去势抵抗前列腺癌患者中具有活性和安全性。

为了比较[177Lu] Lu-PSMA-617与卡巴他赛治疗转移性去势抵抗前列腺癌患者的疗效，研究组在澳大利亚的11个中心进行了一项多中心、非盲、随机、临床2期试验。研究组招募患有转移性去势抵抗前列腺癌的男性，卡巴他赛被认为是下一个合适的标准治疗方法。

参与者需要有足够的肾、血液和肝功能，东部肿瘤协作组的表现状态为0-2，允许此前治疗与雄激素受体定向治疗。男性均接受镓-68 [68Ga]Ga-PSMA-11和2-氟-18[18F]氟-2-脱氧-D-葡萄糖（FDG）PET-CT扫描。试验的PET合格标准为PSMA阳性疾病。将男性参与者按1：1随机分配，分别接受[177Lu] Lu-PSMA-617或卡巴他赛方案治疗。主要终点是前列腺特异性抗原（PSA）反应，比基线至少降低50%。

2018年2月6日至2019年9月3日，研究组对291名男性进行了筛查，其中200名符合PET成像条件。随机分配给[177Lu] Lu-PSMA-617的99名男性中有98名（99%）接受了研究治疗，而随机分配给卡巴他赛的101名男性中有85名（84%）。

[177Lu] Lu-PSMA-617组男性的PSA应答率为66%，显著高于卡巴他赛组（37%）。[177Lu] Lu-PSMA-617组98名男性中有32名（33%）发生3-4级不良事件，而卡巴他赛组85名男性中有45名（53%）。没有发生与[177Lu]Lu-PSMA-617相关的死亡事件。

研究结果表明，对于转移性去势抵抗前列腺癌患者，采用[177Lu]Lu-PSMA-617治疗，与卡巴他赛相比，可导致更高的PSA反应和更少的3级或4级不良事件，值得临床推广。

附：英文原文

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

Author: Michael S Hofman, Louise Emmett, Shahneen Sandhu, Amir Iravani, Anthony M Joshua, Jeffrey C Goh, David A Pattison, Thean Hsiang Tan, Ian D Kirkwood, Siobhan Ng, Roslyn J Francis, Craig Gedye, Natalie K Rutherford, Andrew Weickhardt, Andrew M Scott, Sze-Ting Lee, Edmond M Kwan, Arun A Azad, Shakher Ramdave, Andrew D Redfern, William Macdonald, Alex Guminski, Edward Hsiao, Wei Chua, Peter Lin, Alison Y Zhang, Margaret M McJannett, Martin R Stockler, John A Violet, Scott G Williams, Andrew J Martin, Ian D Davis, Arun A Azad, Wei Chua, Ian D Davis, Nattakorn Dhiantravan, Louise Emmett, Kate Ford, Michael S Hofman, Roslyn J Francis, Craig Gedye, Jeffrey C Goh, Alex Guminski, Edward Hsiao, Amir Iravani, Anthony M Joshua, Ian D Kirkwood, Ailsa Langford, Nicola Lawrence, Sze-Ting Lee, Peter Lin, Andrew J Martin, William McDonald, Margaret M McJannett, Siobhan Ng, David A Pattison, Shakher Ramdave, Nisha Rana, Andrew D Redfern, Natalie K Rutherford, Shahneen Sandhu, Andrew M Scott, Martin R Stockler, Shalini Subramaniam, Thean Hsiang Tan, John A Violet, Andrew Weickhardt, Scott G Williams, Sonia Yip, Alison Y Zhang

Issue&Volume: 2021/02/27

Abstract:

Background

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.

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/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 [ 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.

DOI: 10.1016/S0140-6736(21)00237-3

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)00237-3/fulltext