Characterizing genomic alterations in patients with metastatic urothelial carcinoma (mUC) treated with enfortumab-vedotin (EV) with a focus on 1q23.3.

person Renee Maria Saliby Dana-Farber Cancer Institute, Boston, MA info_outline Renee Maria Saliby, Karl Semaan, Ilana B. Epstein, Sonsoles Liria, Christopher Dall, Eddy Saad, Marc Eid, John Canniff, Lucia Kwak, Stephanie A. Berg, Charlene Mantia, Bradley Alexander McGregor, David A. Braun, Toni K. CHOUEIRI, Joaquim Bellmunt

Authors person Renee Maria Saliby Dana-Farber Cancer Institute, Boston, MA info_outline Renee Maria Saliby, Karl Semaan, Ilana B. Epstein, Sonsoles Liria, Christopher Dall, Eddy Saad, Marc Eid, John Canniff, Lucia Kwak, Stephanie A. Berg, Charlene Mantia, Bradley Alexander McGregor, David A. Braun, Toni K. CHOUEIRI, Joaquim Bellmunt Organizations Dana-Farber Cancer Institute, Boston, MA, CFCE - Dana-Farber Cancer Institute, Boston, MA, Mass General Brigham, Boston, MA, DFCI/PCC Fellowship Program - Attendings, Boston, MA, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, Yale Cancer Center, Yale School of Medicine, New Haven, CT, The Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, MA Abstract Disclosures Research Funding No funding sources reported Background: EV has improved outcomes for patients with mUC whether used as monotherapy or in combination. Limited studies have explored EV's efficacy and toxicity using combined genomic data from multiple platforms. We explored the association of genomic alterations with clinical outcomes in patients with mUC receiving EV treated at a single institution. Methods: Clinical and genomic data from patients with mUC treated with EV at the Dana-Farber Cancer Institute was analyzed. Genomic data was obtained using the targeted Oncopanel platform. Overall survival (OS), progression-free survival (PFS), and toxicity-free survival (TFS) as well as objective response rate (ORR) and progressive disease (PD) as best response according to RECIST 1.1 criteria were studied. Patients were categorized based on genomic alterations employing log-rank tests and univariate Cox regression for OS, PFS, and TFS, and Fisher’s exact test for ORR and PD. Results: We identified 286 patients treated for advanced UC since the approval of EV in 2021, of whom 65 received EV monotherapy, had available genomic data and were included in our analysis. Two genomic regions, 1q23.3 and 9p21.3 were found of interest. 17% (N=11) exhibited gain or amplification at the 1q23.3 cytoband ( PVRL4 cytoband) while 35% (N=23) had a two-copy deletion or loss at 9p21.3 ( MTAP, CDKN2A/B cytoband). While none of the results were statistically significant, gain or amplification of 1q23.3 was associated with a trend towards worse OS (Table). ORR was 29% compared to 60% in those without, but this difference was not statistically significant (p.value = 0.62). Two-copy deletion or loss at 9p21.3 was associated with numerically longer OS (Table) ORR was 57% in patients with the alteration versus 50% in those without, and 9% versus 17% for PD, respectively. These differences also did not reach statistical significance (p.value = 0.46). Conclusions: Our study did not find significant correlations between specific somatic alterations and clinical outcomes in patients with metastatic UC treated with EV though limited by small sample size. The observed trends in alterations of 1q23.3 and 9p21.3 warrant further investigation in larger cohorts. Median OS, PFS and TFS of patients with and without alterations of interest, p.values from log-rank test and HR from Cox regression. Median with Alteration Median without Alteration p.value HR (95%CI) 1q23.3 OS 9.45 21.89 0.15 1.80(0.80-4.04) PFS 7.38 7.19 0.89 0.94(0.46-2.45) TFS 1.65 0.93 0.84 1.23(0.38-1.75) 9p21.3 OS 32.98 15.75 0.55 0.80(0.38-1.67) PFS 7.19 7.58 0.61 1.21(0.59-2.46) TFS 1.19 0.94 0.84 1.06(0.57-1.97)