Genomic Biomarkers Associated with Enfortumab Vedotin Outcomes for Patients with Advanced Urothelial Carcinoma: Analysis of UNITE Study Data

Enfortumab vedotin (EV) is used as monotherapy or combined with pembrolizumab in advanced urothelial carcinoma (aUC), but biomarker data associated with EV outcomes are limited. We identified 170 patients in the UNITE study who received EV monotherapy and had molecular biomarker data available. Outcomes for groups with and without a particular biomarker were compared using logistic regression (unadjusted) for the objective response rate (ORR), and a log-rank test and Cox proportional-hazard models (CPHMs) for progression-free survival (PFS) and overall survival (OS) from EV initiation. Molecular biomarkers were also evaluated in separate multivariable analyses using CPHMs that accounted for clinical characteristics. Median patient age was 70 yr; 78% of the cohort were male and 65% had pure UC histology. Median PFS was shorter for patients with CDKN2A alterations (4.6 vs 6 mo; p = 0.024) and for patients with CDKN2B alterations (4.4 vs 6 mo; p = 0.008). Median OS was longer for patients with high tumor mutational burden (13.6 vs 8.3 mo; p = 0.014). ORR was higher for patients with TSC1 alterations (87% vs 51%; p = 0.018). In multivariable analyses, CDKN2A and CDKN2B alterations were associated with inferior median PFS. This multi-institutional retrospective study of patients with aUC identified potential biomarkers associated with EV monotherapy outcomes that should be further investigated. PATIENT SUMMARY: We investigated genetic changes in urinary tract tumors that might be associated with response to enfortumab vedotin (EV) treatment in patients with advanced disease. Survival after EV treatment was longer for tumors with a higher number of mutations than for tumors with fewer mutations. However, mutations in two genes (CDKN2A and CDKN2B) were associated with worse outcomes after EV treatment. These findings will not affect current clinical practice, but should be investigated further in future studies.

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Journal
European Urology Oncology
Published
2024-12-20
DOI
https://doi.org/10.1016/j.euo.2024.12.006
Citations
6
Primary Topic
Bladder and Urothelial Cancer Treatments
Type
article
Field-Weighted Citation Impact
3.44
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article

Genomic Biomarkers Associated with Enfortumab Vedotin Outcomes for Patients with Advanced Urothelial Carcinoma: Analysis of UNITE Study Data

Omar Alhalabi, Matthew T. Campbell, Cindy Jiang, Ali Raza Khaki et al.
6 citations
European Urology Oncology
Bladder and Urothelial Cancer Treatments
3.44
article

Genomic Biomarkers Associated with Enfortumab Vedotin Outcomes for Patients with Advanced Urothelial Carcinoma: Analysis of UNITE Study Data

Omar Alhalabi, Matthew T. Campbell, Cindy Jiang, Ali Raza Khaki, Rohit Bose, Arnab Basu, Hamid Emamekhoo, Petros D. Grivas, Vadim S. Koshkin, Woogwang Sim, Rafee Talukder, Ajjai Alva, Dory Freeman, Mehmet Asım Bilen, Yousef Zakharia, Sean Evans, Pedro Coelho Barata, Tanya Jindal, Deepak Kilari, Charles B. Nguyen, Matthew P. Davidsohn, Christopher Hoimes, Amanda Nizam, Joaquim Bellmunt, Matthew I. Milowsky, Sumit Shah, Dimitra Rafailia Bakaloudi, Cameron Pywell, Nancy B. Davis, Michael Glover, Shilpa Gupta, Emily Lemke
article en
6 citations

Abstract

Enfortumab vedotin (EV) is used as monotherapy or combined with pembrolizumab in advanced urothelial carcinoma (aUC), but biomarker data associated with EV outcomes are limited. We identified 170 patients in the UNITE study who received EV monotherapy and had molecular biomarker data available. Outcomes for groups with and without a particular biomarker were compared using logistic regression (unadjusted) for the objective response rate (ORR), and a log-rank test and Cox proportional-hazard models (CPHMs) for progression-free survival (PFS) and overall survival (OS) from EV initiation. Molecular biomarkers were also evaluated in separate multivariable analyses using CPHMs that accounted for clinical characteristics. Median patient age was 70 yr; 78% of the cohort were male and 65% had pure UC histology. Median PFS was shorter for patients with CDKN2A alterations (4.6 vs 6 mo; p = 0.024) and for patients with CDKN2B alterations (4.4 vs 6 mo; p = 0.008). Median OS was longer for patients with high tumor mutational burden (13.6 vs 8.3 mo; p = 0.014). ORR was higher for patients with TSC1 alterations (87% vs 51%; p = 0.018). In multivariable analyses, CDKN2A and CDKN2B alterations were associated with inferior median PFS. This multi-institutional retrospective study of patients with aUC identified potential biomarkers associated with EV monotherapy outcomes that should be further investigated. PATIENT SUMMARY: We investigated genetic changes in urinary tract tumors that might be associated with response to enfortumab vedotin (EV) treatment in patients with advanced disease. Survival after EV treatment was longer for tumors with a higher number of mutations than for tumors with fewer mutations. However, mutations in two genes (CDKN2A and CDKN2B) were associated with worse outcomes after EV treatment. These findings will not affect current clinical practice, but should be investigated further in future studies.

European Urology OncologyVol. 8(2)
University of North Carolina at Chapel Hill (US), University of Iowa (US), Cleveland Clinic (US), The University of Texas MD Anderson Cancer Center (US), University of Wisconsin–Madison (US), Emory University (US), Duke University (US), University of California, San Francisco (US), Vanderbilt University (US), University of Washington (US), Medical College of Wisconsin (US), University of Michigan (US), University of Alabama at Birmingham (US), Fred Hutch Cancer Center (US), University of Wisconsin Carbone Cancer Center (US), Dana-Farber Cancer Institute (US), Michigan Center for Translational Pathology (US), University Hospitals Seidman Cancer Center (US), UCSF Helen Diller Family Comprehensive Cancer Center (US), Vanderbilt-Ingram Cancer Center, UNC Lineberger Comprehensive Cancer Center, Stanford University (US)
Openalex Percentile: Top 7%
Bladder and Urothelial Cancer Treatments
3.44
DOIOpen Access PDFOpenAlex
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