铂类药物治疗禁忌的晚期尿路上皮癌患者一线使用 PD1/L1 抑制剂的临床结局。
Clinical Outcomes of Platinum-ineligible Patients with Advanced Urothelial Carcinoma Treated With First-line PD1/L1 Inhibitors.
机构信息
McMaster University, Hamilton, ON, Canada.
St. Vincent Hospital, Worcester, MA.
出版信息
Clin Genitourin Cancer. 2021 Oct;19(5):425-433. doi: 10.1016/j.clgc.2021.04.008. Epub 2021 Apr 20.
BACKGROUND
PD1/L1 inhibitors are approved by FDA as first-line therapy for patients with advanced urothelial carcinoma (aUC) who are cisplatin-ineligible with high tumor PD-L1 expression or are platinum-ineligible regardless of PD-L1 expression. However, the outcomes when employing PD1/L1 inhibitors for platinum-ineligible patients are unclear. This retrospective analysis evaluates the clinical outcomes of first-line PD1/L1 inhibitors in patients with aUC deemed to be platinum-ineligible.
METHODS
Data were retrospectively collected from 8 academic institutions. The following criteria were used to define platinum ineligibility: creatinine clearance (CrCl) < 30 mL/min; Eastern Cooperative Oncology Group (ECOG) performance status (PS) 3; CrCl 30 to 59 mL/min and ECOG PS 2; elderly and/or comorbidities. Patient characteristics, responses and treatment-related toxicities were identified. Survival curves were estimated by the Kaplan-Meier method. A Cox regression analysis was conducted to explore the association of baseline variables with response and survival.
RESULTS
A total of 79 platinum-ineligible patients with aUC were eligible. Patients were treated with atezolizumab (51.9%), pembrolizumab (35.5%), nivolumab (8.9%), or durvalumab (3.8%). The objective response rate was 27.9%. The median overall survival was 45 weeks (95% confidence interval [CI], 32-80), and the median treatment failure-free survival was 16 weeks (95% CI, 9-18). Treatment-related toxicity of any grade and grade ≥ 3 was seen in 41.8% and 31.7% of patients, respectively. Anemia and liver metastasis were associated with worse survival.
CONCLUSION
The efficacy of first-line PD1/L1 inhibitors for platinum-ineligible patients with aUC in the real world appears comparable to those reported in trials of unselected cisplatin-ineligible patients, whereas grade ≥ 3 toxicities appear more common. Further validation is required including data based on PD-L1 status and other biomarkers. Platinum-ineligible patients with aUC warrant evaluation of novel, safe, and effective agents.
背景
PD1/L1 抑制剂已被 FDA 批准作为不适合使用顺铂的晚期尿路上皮癌（aUC）患者的一线治疗药物，这些患者的肿瘤 PD-L1 表达高或无论 PD-L1 表达如何均不适合使用铂类药物。然而，对于不适合使用铂类药物的患者使用 PD1/L1 抑制剂的结果尚不清楚。本回顾性分析评估了不适合使用铂类药物的 aUC 患者一线使用 PD1/L1 抑制剂的临床结果。
方法
数据从 8 个学术机构中进行了回顾性收集。以下标准用于定义不适合使用铂类药物：肌酐清除率（CrCl）<30ml/min；东部合作肿瘤学组（ECOG）表现状态（PS）3；CrCl 为 30 至 59ml/min 且 ECOG PS 为 2；年龄较大和/或合并症。患者特征、反应和与治疗相关的毒性被确定。通过 Kaplan-Meier 法估计生存曲线。进行 Cox 回归分析以探讨基线变量与反应和生存的关系。
结果
共纳入 79 例不适合使用铂类药物的 aUC 患者。患者接受阿特珠单抗（51.9%）、帕博利珠单抗（35.5%）、纳武单抗（8.9%）或度伐利尤单抗（3.8%）治疗。客观缓解率为 27.9%。中位总生存期为 45 周（95%置信区间[CI]，32-80），中位治疗失败无进展生存期为 16 周（95%CI，9-18）。任何级别和≥3 级的治疗相关毒性分别见于 41.8%和 31.7%的患者。贫血和肝转移与较差的生存相关。
结论
在真实世界中，对于不适合使用铂类药物的 aUC 患者，一线 PD1/L1 抑制剂的疗效似乎与未经选择的不适合使用顺铂的患者的临床试验报告相当，而≥3 级毒性似乎更为常见。需要进一步验证，包括基于 PD-L1 状态和其他生物标志物的数据。不适合使用铂类药物的 aUC 患者需要评估新型、安全和有效的药物。
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