Hyperprogressive Disease in Patients With Urothelial Carcinoma or Renal Cell Carcinoma Treated With PD-1/PD-L1 Inhibitors
Hyperprogressive Disease in Patients With Urothelial Carcinoma or Renal Cell Carcinoma Treated With PD-1/PD-L1 Inhibitors
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DOI：
10.1016/j.clgc.2019.09.009
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发表时间：
2020-04-01
影响因子：
3.2
通讯作者：
Lee, Jae Lyun
中科院分区：
文献类型：
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作者：
Hwang, Inhwan;Park, Inkeun;Lee, Jae Lyun
在接受程序性细胞死亡蛋白1/程序性死亡配体1抑制剂治疗的尿路上皮癌和肾细胞癌患者中，高进展性疾病（HPD）的预测因素尚未得到表征。我们对203例连续患者进行了回顾性研究。我们发现HPD的发生率为6.4%，治疗时的肾功能损害和尿路上皮细胞癌与HPD的发生有关。背景：在程序性细胞死亡蛋白1（PD-1）/程序性死亡配体1（PD-L1）抑制剂治疗的早期周期中，观察到一种称为超进展性疾病（HPD）的快速进展模式。关于生殖泌尿系癌症患者的HPD数据有限。患者和方法：我们纳入了2015年2月至2018年6月期间接受PD-1/PD-L1抑制剂治疗的203例泌尿生殖系统癌症患者。HPD定义为肿瘤负荷增加超过50%，肿瘤生长速率增加超过2倍，或出现广泛（10个或更多）新病变。结果：102例肾细胞癌（RCC）患者和101例尿路上皮癌（UC）患者入选。13例（6.4%）患者观察到HPD。疾病进展和HPD患者的中位总生存期分别为7.3个月和3.5个月。UC患者中HPD的发生率高于RCC患者（11.9% vs. 0.9%; P = 0.01）。多因素分析显示UC和肌酐> 1.2 mg/dL是HPD的独立预测因素。PD-1/PD-L1抑制剂治疗后淋巴细胞数量增加30%是HPD的阴性预测因子。接受基于紫杉醇的化疗的UC患者的HPD发生率是接受PD-1/PD-L1抑制剂治疗的患者的三分之一。结论：HPD主要发生于UC患者，而在RCC患者中的发生率可忽略不计。对于肌酐高于1.2 mg/dL的UC患者，应谨慎使用PD-1/PD-L1抑制剂治疗。(C)2019爱思唯尔公司All rights reserved.
The predictive factors of hyperprogressive disease (HPD) in patients with urothelial carcinoma and renal cell carcinoma treated with programmed cell death protein 1/programmed death-ligand 1 inhibitors have not yet been characterized. We performed a retrospective study of 203 consecutive patients. We found the frequency of HPD was 6.4%, and renal impairment at the time of treatment and urothelial cell carcinoma were associated with the occurrence of HPD.Background: A rapid progression pattern called hyperprogressive disease (HPD) has been observed during early cycles of programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitor therapy. Data regarding HPD in patients with genitourinary cancer are limited. Patients and Methods: We included 203 patients with genitourinary cancer treated with PD-1/PD-L1 inhibitors between February 2015 and June 2018. HPD was defined as a greater than 50% increase in tumor burden, greater than 2-fold increase in tumor growth rate, or development of extensive (10 or more) new lesions. Results: Patients (n = 102) with renal cell carcinoma (RCC) and patients (n = 101) with urothelial carcinoma (UC) were included. HPD was observed in 13 (6.4%) patients. The median overall survival for patients with progressive disease and HPD was 7.3 months and 3.5 months, respectively. HPD occurred more frequently in patients with UC than in those with RCC (11.9% vs. 0.9%; P = .01). Multivariate analysis showed that UC and creatinine above 1.2 mg/dL were independent predictive factors for HPD. A 30% increase in lymphocyte number following PD-1/PD-L1 inhibitor treatment was a negative predictor of HPD. The incidence of HPD in patients with UC treated with paclitaxel-based chemotherapy was one-third of those treated with PD-1/PD-L1 inhibitors. Conclusion: HPD developed predominantly in patients with UC, and the incidence of HPD in patients with RCC was negligible. Treatment with PD-1/PD-L1 inhibitors should be prescribed with caution in patients with UC and creatinine above 1.2 mg/dL. (C) 2019 Elsevier Inc. All rights reserved.