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接受阿替利珠单抗治疗的转移性尿路上皮癌患者的预后因素。

Prognostic factors in patients with metastatic urothelial carcinoma who have treated with Atezolizumab.

作者信息

Tural Deniz, Ölmez Ömer Fatih, Sümbül Ahmet Taner, Özhan Nail, Çakar Burcu, Köstek Osman, Ekenel Meltem, Erman Mustafa, Coşkun Hasan Şenol, Selçukbiricik Fatih, Keskin Özge, Türköz Fatma Paksoy, Oruç Kerem, Bayram Selami, Bilgetekin İrem, Yıldız Birol, Şendur Mehmet Ali Nahit, Paksoy Nail, Dirican Ahmet, Erdem Dilek, Selam Meltem, Tanrıverdi Özgür, Paydaş Semra, Urakçı Zuhat, Atağ Elif, Güncan Sabri, Ürün Yüksel, Alkan Ali, Kaya Ali Osman, Özyükseler Deniz Tataroğlu, Taşkaynatan Halil, Yıldırım Mustafa, Sönmez Müge, Başoğlu Tuğba, Gündüz Şeyda, Kılıçkap Saadettin, Artaç Mehmet

机构信息

Department of Medical Oncology, Bakirkoy Dr. Sadi Konuk Training and Research Hospital, Zuhuratbaba District, Tevfik Saglam St. No: 11, Bakirkoy, Istanbul, Turkey.

Medical Oncology, Medipol University Hospital, Istanbul, Turkey.

出版信息

Int J Clin Oncol. 2021 Aug;26(8):1506-1513. doi: 10.1007/s10147-021-01936-6. Epub 2021 May 23.

Abstract

BACKGROUND

Atezolizumab (ATZ) has demonstrated antitumor activity and manageable safety in previous studies of patients with metastatic platinum-resistant urothelial carcinoma. However, the response rate of Atezolizumab was modest. In the current study, we evaluated the pretreatment prognostic factors for overall survival in patients with metastatic urothelial carcinoma who have progressed after first-line chemotherapy in the Expanded-Access Program of Atezolizumab.

PATIENTS AND METHODS

In this study, we present a retrospective analysis of 113 patients with urothelial cancer treated with ATZ after progression on first-line chemotherapy. Data of the patients was obtained from patient files and hospital records. Eligible patients included metastatic urothelial carcinoma patients treated with at least one course of ATZ. Univariate analysis was used to identify clinical and laboratory factors that significantly impact OS. Variables were retained for multivariate analysis if they had a statistical relationship with OS (p  < 0.1), and then included a final model of p  < 0.05.

RESULTS

The median follow-up duration was 23.5 months. Of the patients, 98 (86.7%) were male and 13.3% were female. The median age was 65 years of age (37-86). In univariate analysis, primary tumor location in the upper tract, increasing absolute neutrophil count (ANC), increasing absolute lymphocyte count, neutrophil-to-lymphocyte ratio (NLR) > 3, liver metastases, baseline creatinine clearance less (GFR) than 60 ml/min, Eastern Cooperative Oncology Group (ECOG) performance status (1 ≥), and hemoglobin levels below 10 mg/dl were all the significantly associated with OS. Three of the five adverse prognostic factors according to the Bellmunt criteria were independent of short survival: liver metastases HR 3.105; 95% CI 1.673-5.761; p < (0.001), ECOG PS (1 ≥) HR 2.184; 95% CI 1.120-4.256; p = 0.022, and Hemoglobin level below 10 mg/dl HR 2.680; 95% CI 1.558-4.608; p < (0.001). In addition, NLR > 3 hazard ratio [HR] 2.092; 95% CI 1.031-4.243; p = 0.041 and GFR less than 60 ml/min HR 1.829; 95% CI 1.1-3.041; p = 0.02, maintained a significant association with OS in multivariate analysis.

CONCLUSIONS

This model confirms the Bellmunt model with the addition of NLR > 3 and GFR less than 60 ml/min and can be associated with clinical trials that use immunotherapy in patients with bladder cancer.

摘要

背景

在先前针对转移性铂耐药尿路上皮癌患者的研究中,阿替利珠单抗(ATZ)已显示出抗肿瘤活性且安全性可控。然而,阿替利珠单抗的缓解率一般。在本研究中,我们在阿替利珠单抗扩大可及项目中评估了一线化疗后进展的转移性尿路上皮癌患者总生存的预处理预后因素。

患者与方法

在本研究中,我们对113例一线化疗进展后接受ATZ治疗的尿路上皮癌患者进行了回顾性分析。患者数据来自患者档案和医院记录。符合条件的患者包括接受至少一个疗程ATZ治疗的转移性尿路上皮癌患者。采用单因素分析来确定对总生存有显著影响的临床和实验室因素。如果变量与总生存有统计学关系(p < 0.1),则保留用于多因素分析,然后纳入p < 0.05的最终模型。

结果

中位随访时间为23.5个月。患者中,98例(86.7%)为男性,13.3%为女性。中位年龄为65岁(37 - 86岁)。在单因素分析中,上尿路原发性肿瘤部位、绝对中性粒细胞计数(ANC)增加、绝对淋巴细胞计数增加、中性粒细胞与淋巴细胞比值(NLR)> 3、肝转移、基线肌酐清除率(GFR)低于60 ml/min、东部肿瘤协作组(ECOG)体能状态(≥1)以及血红蛋白水平低于10 mg/dl均与总生存显著相关。根据贝尔蒙特标准的五个不良预后因素中有三个与短生存期独立相关:肝转移HR 3.105;95% CI 1.673 - 5.761;p <(0.001),ECOG PS(≥1)HR 2.184;95% CI 1.120 - 4.256;p = 0.022,以及血红蛋白水平低于10 mg/dl HR 2.680;95% CI 1.558 - 4.608;p <(0.001)。此外,NLR > 3风险比[HR] 2.092;95% CI 1.031 - 4.243;p = 0.041和GFR低于60 ml/min HR 1.829;95% CI 1.1 - 3.041;p = 0.02,在多因素分析中与总生存仍保持显著关联。

结论

该模型在贝尔蒙特模型基础上增加了NLR > 3和GFR低于60 ml/min,可用于膀胱癌患者免疫治疗的临床试验。

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