131I-LNTH-1095 Radioligand Therapy plus Enzalutamide versus Enzalutamide Alone in Men with PSMA-Avid Metastatic Castration-Resistant Prostate Cancer: A Phase II Study.

patients_and_methods

Men ≥18 years with PSMA-positive prostate cancer (PSMA PET tracer uptake >1× liver SUVmean in all CT-measurable lesions) were randomly assigned 2:1 to 131I-LNTH-1095 (4 cycles of 3.7 GBq/dose every 8 weeks) + enzalutamide (160 mg orally once daily) versus enzalutamide alone.

年龄≥18岁的PSMA阳性前列腺癌患者（所有CT可测量病灶的PSMA PET示踪剂摄取量>1×肝脏SUVmean），被随机分配至131I-LNTH-1095（每8周一次，共4个周期，每次剂量为3.7 GBq）+恩杂鲁胺（每日口服160 mg）组与仅恩杂鲁胺组，比例为2:1。

The primary endpoint was PSA50 response.

主要终点是PSA50反应。

Secondary endpoints included radiographic progression-free survival(rPFS), objective response rate, overall survival(OS), and safety.

次要终点包括影像学无进展生存期（rPFS）、客观反应率、总生存（OS）和安全性。

Results

Of 177 screened subjects, 120 were randomly assigned (80: 131I-LNTH-1095 + enzalutamide; 40: enzalutamide monotherapy).

在177名筛查的受试者中，有120名被随机分配（80: 131I-LNTH-1095 + 恩杂鲁胺；40: 恩杂鲁胺单药治疗）。

PSA50 response was 62.9% [95% confidence interval(CI), 50.5-74.1] for 131I-LNTH-1095 + enzalutamide versus 31.3% (16.1-50) for enzalutamide alone (P = 0.003).

PSA50反应率为62.9% [95%置信区间（CI），50.5-74.1] 对于131I-LNTH-1095 + 恩杂鲁胺，而恩杂鲁胺单独治疗的反应率为31.3%（16.1-50）（P = 0.003）。

The median rPFS was 14.0 months (95% CI, 8.64-18.20) for 131I-LNTH-1095 + enzalutamide versus 11.5 months (2.79-18.43) for enzalutamide alone (P = 0.10).

131I-LNTH-1095 + 酮康唑治疗组的中位无进展生存期（rPFS）为14.0个月（95%置信区间，8.64-18.20），而单独使用酮康唑治疗组为11.5个月（2.79-18.43）（P = 0.10）。

The incidenceof grade ≥3 treatment-emergent adverse events (TEAE) was 65.8% for 131I-LNTH-1095 + enzalutamide versus 41% for enzalutamide monotherapy; the most frequent TEAEs were fatigue (75% vs. 53.8%), nausea (59.2% vs. 33.3%), thrombocytopenia (51.3% vs. 0%), and decreased appetite (48.7% vs. 17.9%), respectively.

131I-LNTH-1095 + 酮康唑治疗组的3级及以上治疗相关不良事件（TEAE）发生率为65.8%，而酮康唑单药治疗组为41%；最常见的TEAE分别是疲劳（75%对比53.8%）、恶心（59.2%对比33.3%）、血小板减少（51.3%对比0%）和食欲减退（48.7%对比17.9%）。

Two deaths in the 131I-LNTH-1095 + enzalutamide group were considered treatment-related.

131I-LNTH-1095 + 雄激素受体抑制剂恩杂鲁胺组中有两例死亡被认为是与治疗相关的。

The study was not powered to detect rPFS and OS differences.

该研究没有足够的统计功效来检测放射学无进展生存期（rPFS）和总生存（OS）的差异。

Conclusions

131I-LNTH-1095 + enzalutamide was associated with a statistically significant improvement in PSA50 response compared with enzalutamide alone despite a lower dosing schedule (4 cycles of 3.7 GBq/dose every 8 weeks) than the other approved PSMA RLT agents.

131I-LNTH-1095 加上恩杂鲁胺相较于单独使用恩杂鲁胺，尽管其剂量方案（每8周4个周期，每周期3.7 GBq）低于其他已批准的前列腺特异性膜抗原放射性配体治疗（PSMA RLT）药物，但与显著改善的PSA50反应相关。

Grade ≥3 adverse events were more frequent with combination therapy, particularly hematologic toxicity.

联合治疗的3级或更高级别的不良事件更为频繁，尤其是血液学毒性。