Department of Urology, Campus Lübeck, University Hospital Schleswig-Holstein, Lübeck, Germany.
Medical Oncology Service, Hospital Universitario 12 de Octubre, Madrid, Spain.
J Urol. 2021 Aug;206(2):240-251. doi: 10.1097/JU.0000000000001768. Epub 2021 Apr 9.
Atezolizumab is an established treatment option for pretreated urothelial carcinoma, demonstrating efficacy in phase II/III trials. The SAUL study enrolled a broader patient population to determine safety and efficacy in underrepresented subgroups.
Patients with metastatic urinary tract carcinoma received atezolizumab 1,200 mg every 3 weeks until disease progression, unacceptable toxicity, loss of clinical benefit, or patient/physician decision. The primary endpoint was safety. Efficacy was a secondary endpoint. Analyses by programmed cell death ligand-1 (PD-L1) status, age, Eastern Cooperative Oncology Group performance status (ECOG PS) and renal impairment were prespecified; post hoc analyses explored outcomes by tumor location.
A total of 1,004 patients were enrolled. Subgroup analyses in patients with older age, renal impairment, or upper tract urothelial carcinoma showed safety and efficacy similar to those in patients without these characteristics. Patients with ECOG PS 2 had clinical features typically associated with aggressive disease; median overall survival was 2.3 months versus 10.0 months in patients with ECOG PS0/1. Patients with PD-L1 expression on ≥5% of tumor-infiltrating immune cells tended to have better outcomes than those with <5% PD-L1 expression, although conclusions on the relative efficacy of atezolizumab cannot be drawn from this single-arm study.
The understudied populations included in the SAUL study had similar outcomes to those in more selected populations included in phase II/III trials of atezolizumab, except for those with ECOG PS 2. Age ≥80 years and/or creatinine clearance <30 ml/minute does not preclude administration of atezolizumab; however, treatment risk versus benefit must be carefully assessed in patients with ECOG PS 2.
阿特珠单抗是一种已被确立的治疗选择，可用于预处理的尿路上皮癌，在 II/III 期试验中显示出疗效。SAUL 研究纳入了更广泛的患者人群，以确定在代表性不足的亚组中的安全性和疗效。
转移性尿路上皮癌患者接受阿特珠单抗 1200mg，每 3 周一次，直至疾病进展、无法耐受的毒性、临床获益丧失或患者/医生决定。主要终点是安全性。疗效是次要终点。根据程序性死亡配体-1（PD-L1）状态、年龄、东部合作肿瘤学组表现状态（ECOG PS）和肾功能不全进行了预设分析；事后分析探索了肿瘤部位的结局。
共纳入 1004 例患者。在年龄较大、肾功能不全或上尿路尿路上皮癌患者的亚组分析中，安全性和疗效与无这些特征的患者相似。ECOG PS 2 的患者具有通常与侵袭性疾病相关的临床特征；中位总生存期为 2.3 个月，而 ECOG PS0/1 的患者为 10.0 个月。肿瘤浸润免疫细胞中 PD-L1 表达≥5%的患者的结局往往优于 PD-L1 表达<5%的患者，但从这项单臂研究中不能得出阿特珠单抗相对疗效的结论。
SAUL 研究中纳入的研究人群包括研究人群中未被充分研究的人群，这些人群的结局与阿特珠单抗的 II/III 期试验中更具选择性的人群相似，除了 ECOG PS 2 的患者。年龄≥80 岁和/或肌酐清除率<30ml/min 并不排除使用阿特珠单抗；然而，在 ECOG PS 2 的患者中，必须仔细评估治疗的风险与获益。
