Department of Urology, The Jikei University School of Medicine, 3-25-8 Nishi-shimbashi, Minato-ku, Tokyo, 105-8461, Japan.
Department of Urology, Kameda Medical Center, 929 Higashi-cho, Kamogawa City, Chiba, 296-8602, Japan.
Cancer Immunol Immunother. 2022 Jan;71(1):229-236. doi: 10.1007/s00262-021-02980-x. Epub 2021 Jun 8.
There has been no clinical evidence to justify continued pembrolizumab therapy beyond progression in patients with metastatic urothelial carcinoma (UC).
We conducted a multicenter retrospective study evaluating the clinical efficacy of continued use of pembrolizumab beyond progression in patients with metastatic UC. Data from 51 patients with metastatic UC, who developed progression during second-line pembrolizumab therapy, were analyzed. Progression was defined based on the Immunotherapy Response Evaluation Criteria in Solid Tumors. The outcome was overall survival (OS). The association between continued treatment, OS, and the risk of all-cause mortality was tested using log-rank test, conventional and time-dependent Cox regression models.
No significant difference in patient characteristics was noted between patients continuing pembrolizumab beyond progression (N = 21) and those discontinuing pembrolizumab (N = 30). Median OS was significantly longer in the continuation group (17.8 vs. 8.8 months; P = 0.038). A multivariable conventional Cox regression model identified continued pembrolizumab administration as a significant independent prognostic factor of all-cause mortality (hazard ratio [HR]: 0.21, 95% confidence interval [CI]: 0.05-0.90, P = 0.036), irrespective of the time from treatment initiation to progression and concurrent clinical progression. Further, longer duration of pembrolizumab treatment beyond progression was independently associated with a reduced risk of all-cause mortality in a multivariable time-dependent Cox regression model, when used as a time-dependent variable (HR: 0.07, 95% CI: 0.01-0.45, P = 0.006).
Continued pembrolizumab administration beyond progression might be beneficial in patients with metastatic UC who were clinically stable.
在转移性尿路上皮癌（UC）患者中，疾病进展后继续使用派姆单抗治疗没有临床证据支持。
我们进行了一项多中心回顾性研究，评估了转移性 UC 患者在二线派姆单抗治疗进展后继续使用派姆单抗的临床疗效。分析了 51 名转移性 UC 患者的数据，这些患者在二线派姆单抗治疗期间发生进展。根据实体瘤免疫治疗疗效评价标准（RECIST）定义进展。主要终点是总生存期（OS）。采用对数秩检验、传统 Cox 回归模型和时依 Cox 回归模型检验继续治疗与 OS 和全因死亡率风险的关系。
进展后继续使用派姆单抗（n=21）和进展后停止使用派姆单抗（n=30）的患者在患者特征方面无显著差异。继续治疗组的中位 OS 明显更长（17.8 个月比 8.8 个月；P=0.038）。传统 Cox 多变量回归模型确定进展后继续使用派姆单抗是全因死亡率的独立预后因素（风险比[HR]：0.21，95%置信区间[CI]：0.05-0.90，P=0.036），无论从治疗开始到进展的时间和是否同时出现临床进展。此外，在多变量时依 Cox 回归模型中，将进展后派姆单抗治疗时间作为时依变量时，更长的派姆单抗治疗时间与全因死亡率风险降低独立相关（HR：0.07，95%CI：0.01-0.45，P=0.006）。
对于临床稳定的转移性 UC 患者，疾病进展后继续使用派姆单抗可能有益。
