Genomic Biomarkers Associated with Enfortumab Vedotin Outcomes for Patients with Advanced Urothelial Carcinoma: Analysis of UNITE Study Data.
Tanya Jindal, Cindy Jiang, Omar Alhalabi, Amanda Nizam, Charles Nguyen, Rafee Talukder, Dimitra Bakaloudi, Matthew Davidsohn, Dory Freeman, Michael Glover, Ali Raza Khaki, Sean Evans, Emily Lemke, Rohit Bose, Woogwang Sim, Cameron Pywell, Arnab Basu, Deepak Kilari, Pedro C Barata, Mehmet A Bilen, Yousef Zakharia, Matthew I Milowsky, Sumit A Shah, Joaquim Bellmunt, Petros Grivas, Hamid Emamekhoo, Nancy B Davis, Shilpa Gupta, Christopher Hoimes, Matthew T Campbell, Ajjai Alva, Vadim S Koshkin
Author Information
Tanya Jindal: Helen Diller Family Cancer Center, University of California-San Francisco, San Francisco, CA, USA.
Cindy Jiang: MD Anderson Cancer Center, University of Texas, Houston, TX, USA.
Omar Alhalabi: MD Anderson Cancer Center, University of Texas, Houston, TX, USA.
Amanda Nizam: Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA.
Charles Nguyen: Rogel Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI, USA.
Rafee Talukder: University of Washington, Seattle, WA, USA.
Dimitra Bakaloudi: University of Washington, Seattle, WA, USA.
Matthew Davidsohn: Dana Farber Cancer Center, Boston, MA, USA.
Dory Freeman: Dana Farber Cancer Center, Boston, MA, USA.
Michael Glover: Stanford University, Stanford, CA, USA.
Ali Raza Khaki: Stanford University, Stanford, CA, USA.
Sean Evans: Winship Cancer Institute, Emory University, Atlanta, GA, USA.
Emily Lemke: Medical College of Wisconsin, Milwaukee, WI, USA.
Rohit Bose: Helen Diller Family Cancer Center, University of California-San Francisco, San Francisco, CA, USA.
Woogwang Sim: Helen Diller Family Cancer Center, University of California-San Francisco, San Francisco, CA, USA.
Cameron Pywell: University of Alabama, Birmingham, AL, USA.
Arnab Basu: University of Alabama, Birmingham, AL, USA.
Deepak Kilari: Medical College of Wisconsin, Milwaukee, WI, USA.
Pedro C Barata: Seidman Cancer Center, University Hospitals, Cleveland, OH, USA.
Mehmet A Bilen: Winship Cancer Institute, Emory University, Atlanta, GA, USA.
Yousef Zakharia: University of Iowa, Iowa City, IA, USA.
Matthew I Milowsky: Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA.
Sumit A Shah: Stanford University, Stanford, CA, USA.
Joaquim Bellmunt: Dana Farber Cancer Center, Boston, MA, USA.
Petros Grivas: Fred Hutchinson Cancer Center, University of Washington, Seattle, WA, USA.
Hamid Emamekhoo: Carbone Cancer Center, University of Wisconsin, Madison, WI, USA.
Nancy B Davis: Vanderbilt-Ingram Cancer Center, Nashville, TN, USA.
Shilpa Gupta: Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA.
Christopher Hoimes: Duke University, Durham, NC, USA.
Matthew T Campbell: MD Anderson Cancer Center, University of Texas, Houston, TX, USA.
Ajjai Alva: Rogel Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI, USA.
Vadim S Koshkin: Helen Diller Family Cancer Center, University of California-San Francisco, San Francisco, CA, USA. Electronic address: vadim.koshkin@ucsf.edu.
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.
