Impact of Histology on Clinical Outcomes of Pembrolizumab Monotherapy in Patients With Advanced or Metastatic Urothelial Carcinoma in the Phase 3 KEYNOTE-045 and KEYNOTE-361 Trials

IF 2.3 3区医学 Q3 ONCOLOGY

Clinical genitourinary cancer Pub Date : 2024-11-15 DOI:10.1016/j.clgc.2024.102273

Patrizia Giannatempo , Jean-Pascal Machiels , Naoto Sassa , Jose Angel Arranz , Yasuhisa Fujii , Wen-Pin Su , Bhumsuk Keam , Stéphane Culine , Ying-Chun Shen , José Muñoz Langa , David Sarid , Maureen Aarts , Fabio Calabrò , Eli Rosenbaum , Blanca Homet Moreno , Abhishek Bavle , Jin Z. Xu , Sun Young Rha

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引用次数: 0

Abstract

Introduction

A post hoc analysis of efficacy and safety outcomes with pembrolizumab monotherapy was conducted in patients with advanced or metastatic urothelial carcinoma (UC) with pure transitional cell carcinoma (TCC) or mixed predominant TCC histology enrolled in the phase 3 KEYNOTE-045 and KEYNOTE-361 studies.

Methods

Adults with platinum-refractory advanced or metastatic UC who received pembrolizumab monotherapy in KEYNOTE-045 and adults with advanced or metastatic UC and no prior systemic chemotherapy who received pembrolizumab monotherapy in KEYNOTE-361 were analyzed separately. Pembrolizumab 200 mg was administered intravenously every 3 weeks for ≤2 years. Histology was assessed by investigator. End points included objective response rate (ORR), progression-free survival, and duration of response per RECIST v1.1 by central radiology assessment, as well as overall survival (OS) and safety.

Results

In KEYNOTE-045, 268 patients had known histology (pure TCC: 186; mixed predominant TCC: 82). At data cutoff (October 1, 2020), median follow up was 62.9 months (range, 59.0-70.9). For pure TCC, confirmed ORR was 21.0% (95% CI, 15.4-27.5); median OS was 9.7 months (95% CI, 7.5-11.8). For mixed predominant TCC, confirmed ORR was 24.4% (95% CI, 15.6-35.1); median OS was 11.6 months (95% CI, 7.4-16.4). In KEYNOTE-361, 307 patients had known histology (pure TCC: 280; mixed predominant TCC: 27). At data cutoff (April 29, 2020), median follow-up was 32.5 months (range, 22.0-42.3). For pure TCC, confirmed ORR was 29.3% (95% CI, 24.0-35.0); median OS was 14.8 months (95% CI, 11.8-17.9). For mixed predominant TCC, confirmed ORR was 40.7% (95% CI, 22.4-61.2); median OS was 16.2 months (95% CI, 5.5-NR). Grade 3-5 treatment-related adverse events occurred at similar rates for treated patients in both studies.

Conclusion

In this post hoc analysis, efficacy and safety outcomes with pembrolizumab monotherapy were generally consistent for patients with advanced or metastatic UC in KEYNOTE-045 and KEYNOTE-361 studies between histology subgroups.

Clinical Trial Registration

ClinicalTrials.gov, KEYNOTE-045 (NCT02256436) and KEYNOTE-361 (NCT02853305)

查看原文本刊更多论文

KEYNOTE-045和KEYNOTE-361期临床试验中，组织学对派姆单抗单药治疗晚期或转移性尿路上皮癌患者临床结果的影响

在iii期KEYNOTE-045和KEYNOTE-361研究中，对晚期或转移性尿路上皮癌（UC）合并纯移行细胞癌（TCC）或混合主导TCC组织学的患者进行了pembrolizumab单药治疗的疗效和安全性结果的回顾性分析。方法分别对KEYNOTE-045中接受派姆单抗单药治疗的铂难治晚期或转移性UC的成人患者和KEYNOTE-361中接受派姆单抗单药治疗的未接受全身化疗的晚期或转移性UC的成人患者进行分析。Pembrolizumab 200mg每3周静脉给予≤2年。由研究者评估组织学。终点包括中心放射学评估的客观缓解率（ORR）、无进展生存期和根据RECIST v1.1的缓解持续时间，以及总生存期（OS）和安全性。结果KEYNOTE-045中，已知组织学的患者268例(纯TCC 186例；混合优势TCC: 82)。截至数据截止日期（2020年10月1日），中位随访时间为62.9个月（范围59.0-70.9）。对于纯TCC，确诊的ORR为21.0% (95% CI, 15.4-27.5)；中位OS为9.7个月（95% CI, 7.5-11.8）。对于混合型显性TCC，确诊ORR为24.4% (95% CI, 15.6-35.1)；中位OS为11.6个月（95% CI, 7.4-16.4）。KEYNOTE-361中，307例患者有已知的组织学(纯TCC: 280例；混合优势TCC: 27)。截至数据截止（2020年4月29日），中位随访时间为32.5个月（范围22.0-42.3个月）。对于纯TCC，确诊的ORR为29.3% (95% CI, 24.0-35.0)；中位OS为14.8个月（95% CI, 11.8-17.9）。对于混合型显性TCC，确诊ORR为40.7% (95% CI, 22.4-61.2)；中位OS为16.2个月（95% CI, 5.5-NR）。在两项研究中，3-5级治疗相关不良事件在接受治疗的患者中发生率相似。在KEYNOTE-045和KEYNOTE-361研究中，组织学亚组间晚期或转移性UC患者采用派姆单抗单药治疗的疗效和安全性基本一致。临床试验注册网站clinicaltrials .gov, KEYNOTE-045 （NCT02256436）和KEYNOTE-361 （NCT02853305）

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来源期刊

Clinical genitourinary cancer 医学-泌尿学与肾脏学

CiteScore

5.20

自引率

6.20%

发文量

201

审稿时长

54 days

期刊介绍： Clinical Genitourinary Cancer is a peer-reviewed journal that publishes original articles describing various aspects of clinical and translational research in genitourinary cancers. Clinical Genitourinary Cancer is devoted to articles on detection, diagnosis, prevention, and treatment of genitourinary cancers. The main emphasis is on recent scientific developments in all areas related to genitourinary malignancies. Specific areas of interest include clinical research and mechanistic approaches; drug sensitivity and resistance; gene and antisense therapy; pathology, markers, and prognostic indicators; chemoprevention strategies; multimodality therapy; and integration of various approaches.