Clinical efficacy analysis of patients (pts) with HER-2 expressing metastatic urothelial carcinoma (mUC) treated with enfortumab vedotin (EV).

person Cindy Jiang MD Anderson Hematology/Oncology Fellowship, Houston, TX info_outline Cindy Jiang, Omar Alhalabi, Jaime Haro-Silerio, Wei Qiao, Amishi Yogesh Shah, Arlene O. Siefker-Radtke, Jianjun Gao, Sangeeta Goswami, Ajjai Shivaram Alva, Vadim S. Koshkin, Charles Guo, Matthew T. Campbell

Authors person Cindy Jiang MD Anderson Hematology/Oncology Fellowship, Houston, TX info_outline Cindy Jiang, Omar Alhalabi, Jaime Haro-Silerio, Wei Qiao, Amishi Yogesh Shah, Arlene O. Siefker-Radtke, Jianjun Gao, Sangeeta Goswami, Ajjai Shivaram Alva, Vadim S. Koshkin, Charles Guo, Matthew T. Campbell Organizations MD Anderson Hematology/Oncology Fellowship, Houston, TX, The University of Texas MD Anderson Cancer Center, Houston, TX, Baylor College of Medicine, Houston, TX, MD Anderson Cancer Center, Houston, TX, University of Texas MD Anderson Cancer Center, Houston, TX, Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, Department of Internal Medicine, Division of Hematology and Oncology, University of Michigan, Ann Arbor, MI, Division of Hematology and Oncology, Department of Medicine,University of California San Francisco, San Francisco, CA Abstract Disclosures Research Funding No funding received None. Background: EV, an antibody drug conjugate (ADC) targeting NECTIN-4, is an approved salvage treatment for unselected pts with mUC. ADCs targeting the human epidermal growth factor receptor-2 (HER-2) have also shown robust activity in clinical trials for mUC with tumor HER-2 expression. We investigated the interaction between HER-2 expression and clinical outcomes of pts treated with EV, which are currently unknown. Methods: We conducted a retrospective, single institution study analyzing pts with mUC who received EV. Immunohistochemistry (IHC) staining for HER-2 was completed with PATHWAY anti-HER2 (4B5) Antibody (Ventana Medical Systems, Tucson, AZ) using established breast cancer scoring algorithm. Wilcoxon rank sum and Fisher exact tests were used to compare continuous and categorical variables, respectively. Cox proportional hazards regression model was used to evaluate a variable’s ability to predict overall survival (OS). Variables with p-value ≤0.1 were included in the multivariate analysis (MVA). Results: We identified 158 pts with mUC who received EV. Median age at EV start was 70 (IQR 66-76), most pts were Caucasian (144, 91%), male (108, 68%), primary bladder tumors (113, 72%), and pure urothelial histology (95, 60%). 96 pts (61%) received prior platinum therapy and 117 pts (74%) had prior immunotherapy. ECOG scores ≥2 was seen in 54 pts (39%) while 75 pts (54%) had Bellmunt scores ≥2 (54%). Median follow up time was 12.5 months and median OS from EV start was 13 months. 94 pts (60%) had HER2 IHC staining. There was no association between HER2 intensity and any of the clinical variables. On univariate analysis (UVA): HER2 3 vs HER2 ≤2 HR was 0.38 (0.14, 0.98), male vs female HR=1.56 (0.94, 2.58), ECOG ≤1 vs ≥2 HR=0.6 (0.38,0.95), Bellmunt score 0-1 vs 2-3 HR=0.49 (0.3, 0.78), and hemoglobin (Hgb) HR=0.75 (0.67, 0.85). MVA showed HER2 3 vs HER2 ≤2 HR was 0.42 (0.16, 1.12), male vs female HR=2.3 (1.17, 4.42), ECOG ≤1 vs ≥2 HR=0.56 (0.30, 1.05), and Hgb HR=0.77 (0.65, 0.92). Conclusions: MVA of this single-site retrospective cohort did not show any association between HER2 expression and survival outcomes in pts with mUC who received EV. Further studies are needed to continue assessing the role of HER2 as a potential prognostic and predictive biomarker in UC, especially if HER-2 directed therapies become incorporated in the mUC treatment paradigm. Characteristic HR (95% CI) p-value Sex: male vs female 1.56 (0.94,2.58) 0.09 Number of prior lines: ≤2 vs. ≥3 1.17 (0.71,1.94) 0.53 Primary Tumor: Bladder vs. other 1.1 (0.68,1.76) 0.71 Liver Metastasis: no vs. yes 0.73 (0.47,1.15) 0.18 ECOG: ≤1 vs. ≥2 0.6 (0.38,0.95) 0.03 HER2 Intensity: 3 vs. ≤2 0.38 (0.14, 0.98 0.05 Bellmunt Score: 0-1 vs. 2-3 0.49 (0.3,0.78) <0.01 Age at initial diagnosis 0.99 (0.97,1.02) 0.58 Hgb 0.75 (0.67,0.85) <0.01