Background

Atezolizumab (anti–programmed death-ligand 1) was approved in the USA, Europe, and elsewhere for treatment-naive and platinum-treated locally advanced/metastatic urothelial carcinoma (mUC).

Objective

To report efficacy and safety from an atezolizumab expanded access study.

Design, setting, and participants

This single-arm, open-label study enrolled 218 patients at 36 US sites. Key eligibility criteria included progression during/following ≥1 platinum-based chemotherapy for mUC or in perioperative setting (progression within 12 mo) and Eastern Cooperative Oncology Group performance status (ECOG PS) 0–2.

Intervention

Patients received atezolizumab1200 mg intravenously every 3 wk until loss of clinical benefit, unacceptable toxicity, consent withdrawal, decision to discontinue, death, atezolizumab commercial availability, or study closure.

Outcome measurements and statistical analysis

Key end points reported herein included Response Evaluation Criteria in Solid Tumors v1.1 objective response rate and duration, disease control rate (DCR; response or stable disease), and safety.

Results and limitations

All patients received prior systemic therapy (68% mUC; 27% adjuvant; and 26% neoadjuvant). At baseline, 57% of 214 treated patients had ECOG PS ≥1, 19% had hemoglobin <10 g/dl, and 25% had liver metastases. Median treatment duration was 9 wk (interquartile range [IQR], 6–12 wk). Median follow-up duration was 2.3 mo (IQR, 1.6–3.4 mo) overall and 2.7 mo (IQR, 2.0–3.5 mo) in patients not known to have died. Seventeen of 114 evaluable patients (15%) had objective responses (16 ongoing at study termination). DCR was 49%. Treatment-related adverse events (mostly fatigue) occurred in 98 of 214 treated patients.

Conclusions

The benefit/risk profile of atezolizumab was consistent with that observed in previous studies, despite pretreatment and poor prognostic factors. These results suggest a potential role for atezolizumab in a broader patient range than typically eligible for phase 1–3 studies.

Patient summary

In this expanded access study, atezolizumab was active and tolerable in a range of patients with platinum-treated metastatic urothelial carcinoma.

中文翻译：

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Atezolizumab在铂类药物治疗的局部晚期或转移性尿道上皮癌中的应用：来自美国的扩大获取研究的临床经验

背景

Atezolizumab（抗程序性死亡配体1）已在美国，欧洲和其他地区获准用于未经治疗和未经铂治疗的局部晚期/转移性尿路上皮癌（mUC）。

客观的

要从atezolizumab扩展访问研究中报告疗效和安全性。

设计，设置和参与者

这项单臂，开放标签的研究在美国36个地点招募了218名患者。关键的入选标准包括：在进行mUC或围手术期≥1的铂类化疗期间/之后或在围手术期（进展在12 mo以内）的进展以及东部合作肿瘤小组的工作状态（ECOG PS）0–2。

干涉

患者每3周静脉注射atezolizumab1200 mg，直到失去临床益处，不可接受的毒性，同意撤消，决定停药，死亡，atezolizumab的商业可得性或研究结束。

成果测量和统计分析

本文报道的关键终点包括实体瘤反应评估标准v1.1客观反应率和持续时间，疾病控制率（DCR；反应或稳定疾病）和安全性。

结果与局限性

所有患者均接受了先前的全身治疗（68％mUC； 27％辅助剂； 26％新辅助剂）。基线时，在214名接受治疗的患者中，有57％的ECOG PS≥1，血红蛋白<10 g / dl的患者19％，肝转移的患者25％。中位治疗持续时间为9周（四分位间距[IQR]，6-12周）。总体中位随访时间为2.3 mo（IQR，1.6-3.4 mo），未知死亡患者为2.7 mo（IQR，2.0-3.5 mo）。114名可评估的患者中有17名（15％）有客观反应（研究终止时有16名正在进行中）。DCR为49％。214名接受治疗的患者中有98名发生了与治疗相关的不良事件（主要是疲劳）。

结论

尽管有预处理和不良预后因素，但atezolizumab的获益/风险状况与之前的研究一致。这些结果表明，与通常需要进行1-3期研究的患者相比，atezolizumab在更广泛的患者范围内具有潜在的作用。

病人总结

在这项扩展的研究中，atezolizumab在铂治疗的转移性尿路上皮癌患者中是活跃且可耐受的。