[177Lu]-PSMA-617-PSMA-617 in oligometastatic hormone sensitive prostate cancer (BULLSEYE): an open-label, randomised, phase 2 study.

Here, we aimed to evaluate 177Lu-PSMA-617 in patients with PSMA-expressing oligometastatic hormone-sensitive prostate cancer (HSPC).

在这里，我们的目标是评估177Lu-PSMA-617在表达PSMA的寡转移性激素敏感性前列腺癌(HSPC)患者中的效果。

Methods

BULLSEYE was an open-label, randomised, phase 2 trial in three academic hospitals in the Netherlands (Radboud University Medical Center, University Medical Center Groningen, and University Medical Center Amsterdam) and one community hospital in Cyprus (German Oncology Center).

BULLSEYE 是一项在荷兰三家学术医院（拉德堡德大学医学中心、格罗宁根大学医学中心和阿姆斯特丹大学医学中心）以及塞浦路斯的一家社区医院（德国肿瘤中心）进行的开放标签、随机、二期试验。

Eligible participants were men, aged 18 years or older, with biochemically recurrent prostate cancer following radical prostatectomy or radiotherapy, Eastern Cooperative Oncology Group performance status score of 0-1, a PSA doubling time of less than 6 months and PSA amounts of over 1·0 μg/L.

符合条件的参与者为年龄在18岁或以上的男性，患有生化复发性前列腺癌，经过根治性前列腺切除术或放射治疗后，东部肿瘤协作组表现状态评分为0-1，前列腺特异性抗原（PSA）倍增时间少于6个月，且PSA量超过1·0 μg/L。

Paients aged 18 years or older with recurrent hormone sensitive prostate cancer following radical surgery or radiotherapy were randomly asigned (1:1) using a centralised web-based system with block randomisation to 177Lu-PSMA-617 (intervention) or standard of care (control) of deferred androgen deprivation therapy (ADT).

年龄在18岁或以上的患者，患有复发性激素敏感性前列腺癌，在接受根治性手术或放疗后，使用中心化的基于网络的系统进行随机分组（1:1），分配到177Lu-PSMA-617（干预组）或延迟雄激素剥夺治疗（ADT）的标准治疗（对照组）。

The treatment group received two cycles of 7·4 GBq 177Lu-PSMA-617 every 6 weeks. 6 weeks after the second treatment cycle, patients with residual PSMA-expressing disease on PSMA-PET-CT, and no grade 3 or worse treatment-related adverse events received two additional cycles of 7·4 GBq 177Lu-PSMA-617 given 6 weeks apart.The control group did not receive treatment but underwent active monitoring for disease progression.

治疗组接受了每6周一次，每次7.4 GBq的177Lu-PSMA-617两个周期的治疗。在第二个治疗周期结束后的6周，如果患者在PSMA-PET-CT上仍有PSMA表达的疾病残留，并且没有3级或更严重的治疗相关不良事件，他们将再接受两次7.4 GBq的177Lu-PSMA-617治疗，两次治疗间隔6周。对照组没有接受治疗，但进行了疾病的进展监测。

Co-primary endpoints were the proportion of patients with disease progression, and time to disease progression with the same endpoint.

主要终点是疾病进展的患者比例，以及达到相同终点的疾病进展时间。

Primary, secondary, and safety endpoints were assessed in the per-protocol population, who all received at least one 1 dose of 177Lu-PSMA-617.

主要终点、次要终点和安全性终点在符合方案的人群中进行了评估，所有这些人都至少接受了一剂177Lu-PSMA-617治疗。

This trial is registered with ClinicalTrials.gov (NCT04443062) and has completed accrual.

该试验已在ClinicalTrials.gov上注册（NCT04443062），并已完成患者招募。

Results

Between April 20, 2020, and July 29, 2024, 78 males were screened and 58 were eligible (29 intervention and 29 control). 56 patients were white, one was Asian, and one was African.

在2020年4月20日至2024年7月29日期间，共有78名男性接受了筛查，其中58名符合入选标准（29名干预组和29名对照组）。56名患者为白人，1名为亚洲人，1名为非洲人。

Patients in the intervention group received a median of four cycles (IQR 4-4) of 177Lu-PSMA-617.

在数据截止日期（2025年3月31日），中位随访时间为27个月（四分位数间距18-32个月）。

At data cutoff (March 31, 2025), median follow-up time was 27 months (IQR 18-32).

在数据截止日期（2025年3月31日），中位随访时间为27个月（四分位数间距18-32）。

During the first 30 weeks, disease progression was reported in two (7%) of 29 patients in the intervention group versus 27 (93%) of 29 patients in the control group (p<0·0001).

在最初的30周内，干预组的29名患者中有2名（7%）报告疾病进展，而对照组的29名患者中有27名（93%）报告疾病进展（p<0·0001）。

Median progression-free survival(per-protocol) was 25 months (IQR 15 to not reached) for intervention group versus 5 months (IQR 3-7) for control (hazard ratio[HR] 0·07, 95% CI 0·03-0·17; p<0·0001).

干预组的中位无进展生存期（按方案）为25个月（四分位数间距15至未达到），而对照组为5个月（四分位数间距3-7）（风险比[HR] 0·07，95%置信区间0·03-0·17；p<0·0001）。

One (3%) patient in the intervention group developed grade 3 dry eyes, which resolved with supportive treatment, and grade 3 lymphocyte count decrease was observed in three (10%) patients in the treatment group.

干预组中有一名（3%）患者发展为3级干眼症，通过支持性治疗得到缓解，治疗组中有三名（10%）患者观察到3级淋巴细胞计数减少。

The control group had five (17%) patients with grade 3 hypertension, one (3%) patient with a grade 3 decrease in lymphocyte count, one (3%) patient with a grade 4 gallbladder infection, and one (3%) patient with a grade 4 myocardial infarction.

对照组中有五名（17%）患者出现3级高血压，一名（3%）患者出现3级淋巴细胞计数减少，一名（3%）患者出现4级胆囊感染，以及一名（3%）患者出现4级心肌梗死。

There were no treatment-related grade 4 adverse events or deaths.

未观察到与治疗相关的4级不良事件或死亡。

No serious adverse events were reported in patients who received 177Lu-PSMA-617.

接受177Lu-PSMA-617治疗的患者中未报告严重不良事件。

The most common adverse events were grade 1 dry mouth in 19 (66%) patients in the treatment group versus three (10%) patients in the control group, fatigue in 16 (55%) patients in the treatment group versus six (21%) patients in the control group, and nausea in 14 (48%) patients in the treatment group versus three (10%) patients in the control group.

最常见的不良事件是治疗组中19名（66%）患者出现1级口干，对照组中3名（10%）患者出现；治疗组中16名（55%）患者出现疲劳，对照组中6名（21%）患者出现；治疗组中14名（48%）患者出现恶心，对照组中3名（10%）患者出现。

No deaths were attributed to the treatment in either group.

两组中均无因治疗导致的死亡事件。

interpretation

177Lu-PSMA-617 showed promising response rates and delayed disease progression in patients with oligometastatic HSPC in this trial. In addition, most treatment-related adverse events were low grade.

177Lu-PSMA-617在本试验中对寡转移性去势抵抗性前列腺癌患者显示出有希望的反应率，并延迟了疾病进展。此外，大多数与治疗相关的不良事件为低级别。

funding

Dutch Prostate Cancer Foundation (Prostaatkankerstichting) and Novartis.

荷兰前列腺癌基金会（Prostaatkankerstichting）和诺华制药。