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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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)

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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.