Impact of Squamous Histology on Clinical Outcomes and Molecular Profiling in Metastatic Urothelial Carcinoma Patients Treated With Immune Checkpoint Inhibitors or Enfortumab Vedotin.

Autor: Jindal T; Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA., Zhang L; Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA., Deshmukh P; Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA., Reyes K; Department of Medicine, School of Medicine, University of California San Francisco, San Francisco, CA., Chan E; Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA., Kumar V; Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA., Zhu X; Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA., Maldonado E; Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA., Feng S; Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA., Johnson M; Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA., Angelidakis A; Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA., Kwon D; Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA., Desai A; Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA., Borno HT; Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA., Bose R; Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA., Wong A; Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA., Hong J; Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA., Carroll P; Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA., Meng M; Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA., Porten S; Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA., Aggarwal R; Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA., Small EJ; Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA., Fong L; Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA., Chou J; Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA., Friedlander T; Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA., de Kouchkovsky I; Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA. Electronic address: Ivan.DeKouchkovsky@ucsf.edu., Koshkin VS; Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA. Electronic address: Vadim.koshkin@ucsf.edu.
Jazyk: angličtina
Zdroj: Clinical genitourinary cancer [Clin Genitourin Cancer] 2023 Oct; Vol. 21 (5), pp. e394-e404. Date of Electronic Publication: 2023 May 17.
DOI: 10.1016/j.clgc.2023.05.007
Abstrakt: Introduction: Urothelial carcinoma with squamous differentiation (UCS) is associated with increased resistance to chemotherapy, but outcomes associated with newer therapies approved in this space over the last 5 to 10 years are less well defined. We investigated clinical outcomes and molecular profiling of patients with UCS treated with an immune checkpoint inhibitor (ICI) and/or Enfortumab vedotin (EV).
Patients and Methods: We undertook a retrospective analysis of UC patients treated with ICI and/or EV. Objective response rate (ORR), progression free survival (PFS) and overall survival (OS) were compared between pure UC (pUC) and UCS using X 2 and log-rank tests, respectively. Prevalence of the most commonly detected somatic alterations were also compared between the 2 histologic subgroups.
Results: A total of 160 patients (40 UCS, 120 pUC) were identified for this analysis. Among 151 patients treated with ICI (38 UCS, 113 pUC), UCS patients had a shorter mPFS (1.9 vs. 4.8 months, P < 0.01) and mOS (9.2 vs. 20.7 months, P < 0.01) compared to pUC. Among 37 patients treated with EV (12 UCS, 25 pUC), UCS patients had a lower ORR (17% vs. 70%, P < 0.01) and shorter mPFS (3.4 vs. 15.8 months, P < 0.01). UCS samples were enriched for CDKN2A, CDKN2B, PIK3CA, while pUC samples were enriched for ERBB2 alterations.
Conclusion: In this single-center retrospective analysis, patients with UCS had a distinct somatic genomic profile relative to patients with pUC. Patients with UCS also had inferior outcomes to ICIs and EV compared to patients with pUC.
(Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE