City of Hope Comprehensive Cancer Center, Duarte, CA, USA.
Sidney Kimmel Cancer Center at Jefferson, Philadelphia, PA, USA.
Eur Urol. 2018 May;73(5):800-806. doi: 10.1016/j.eururo.2018.02.010. Epub 2018 Feb 22.
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).
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.
Patients received atezolizumab1200mg intravenously every 3 wk until loss of clinical benefit, unacceptable toxicity, consent withdrawal, decision to discontinue, death, atezolizumab commercial availability, or study closure.
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.
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 <10g/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.
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.
In this expanded access study, atezolizumab was active and tolerable in a range of patients with platinum-treated metastatic urothelial carcinoma.
阿替利珠单抗（抗程序性死亡配体 1）已在美国、欧洲和其他地区获批用于治疗初治和铂类治疗的局部晚期/转移性尿路上皮癌（mUC）。
报告阿替利珠单抗扩展使用研究的疗效和安全性。
设计、地点和参与者：这项单臂、开放标签研究在美国 36 个地点招募了 218 名患者。主要入选标准包括 mUC 患者在接受≥1 种基于铂类的化疗期间/之后进展（治疗 12 个月内进展）或围手术期进展（12 个月内进展）和东部肿瘤协作组体能状态（ECOG PS）0-2。
患者接受阿替利珠单抗 1200mg 静脉输注，每 3 周 1 次，直至临床获益丧失、不可接受的毒性、同意退出、决定停药、死亡、阿替利珠单抗商业供应或研究关闭。
本报告中的主要终点包括实体瘤反应评价标准 1.1 客观缓解率和缓解持续时间、疾病控制率（DCR；缓解或疾病稳定）和安全性。
所有患者均接受过系统治疗（68%为 mUC；27%为辅助治疗；26%为新辅助治疗）。在基线时，214 名治疗患者中有 57%的 ECOG PS ≥1，19%的血红蛋白<10g/dl，25%的有肝转移。中位治疗持续时间为 9 周（四分位距[IQR]，6-12 周）。总体中位随访时间为 2.3 个月（IQR，1.6-3.4 个月），在已知未死亡的患者中为 2.7 个月（IQR，2.0-3.5 个月）。114 名可评估患者中有 17 名（15%）有客观缓解（16 名在研究结束时仍在持续缓解）。DCR 为 49%。198 名治疗患者中有 98 名（98%）发生与治疗相关的不良事件（主要为疲劳）。
尽管存在预处理和预后不良因素，但阿替利珠单抗的获益/风险特征与先前研究观察到的一致。这些结果表明，阿替利珠单抗在比通常适合 1-3 期研究的患者更广泛的患者范围内可能具有作用。
在这项扩展使用研究中，阿替利珠单抗在一系列铂类治疗的转移性尿路上皮癌患者中具有活性且可耐受。
