Early clinical data indicate that some patients with castration-resistant prostate cancer may benefit from program death ligand-1 (PD-L1) inhibition, especially with enzalutamide. The IMbassador250 trial (no. NCT03016312) enrolled 759 men with metastatic castration-resistant prostate cancer whose disease progressed on abiraterone. The addition of atezolizumab to enzalutamide in an open-label randomized trial did not meet the primary endpoint of improved overall survival in unselected patients (stratified hazard ratio 1.12, 95% confidence interval (0.91, 1.37), P = 0.28), despite an acceptable safety profile. In archival tumor samples, prostate tumors showed comparatively low expression of key immune biomarkers. DNA damage-response alterations, phosphatase and tensin homolog status and PD-L1 expression levels were similar between hormone-sensitive and castration-resistant prostate cancers. In planned biomarker analysis, longer progression-free survival was seen with atezolizumab in patients with high PD-L1 IC2/3, CD8 expression and established immune gene signatures. Exploratory analysis linked progression-free survival in the atezolizumab arm with immune genes such as CXCL9 and TAP1, together with other potentially relevant biomarkers including phosphatase and tensin homolog alterations. Together these data indicate that the expected biology associated with response to immune checkpoint inhibitors is present in prostate cancer, albeit in fewer patients. Careful patient selection may be required for immune checkpoint inhibitors to identify subgroups of patients who may benefit from this treatment approach.

早期临床数据表明，一些去势抵抗性前列腺癌患者可能受益于程序死亡配体-1 (PD-L1) 抑制，尤其是恩杂鲁胺。IMbassador250 试验（编号 NCT03016312）招募了 759 名接受阿比特龙治疗后疾病进展的转移性去势抵抗性前列腺癌患者。在一项开放标签随机试验中，在恩杂鲁胺中加入 atezolizumab 未达到改善未选择患者总生存期的主要终点（分层风险比 1.12，95% 置信区间 (0.91，1.37)，P = 0.28)，尽管安全性可接受。在存档的肿瘤样本中，前列腺肿瘤显示关键免疫生物标志物的表达相对较低。DNA 损伤反应改变、磷酸酶和张力蛋白同系物状态以及 PD-L1 表达水平在激素敏感性和去势抵抗性前列腺癌之间相似。在计划的生物标志物分析中，在具有高 PD-L1 IC2/3、CD8 表达和确定的免疫基因特征的患者中，使用阿替利珠单抗观察到更长的无进展生存期。探索性分析将 atezolizumab 组的无进展生存期与CXCL9和TAP1等免疫基因联系起来，以及其他可能相关的生物标志物，包括磷酸酶和张力蛋白同系物改变。这些数据共同表明，与免疫检查点抑制剂反应相关的预期生物学存在于前列腺癌中，尽管患者较少。免疫检查点抑制剂可能需要仔细选择患者，以确定可能受益于这种治疗方法的患者亚组。