Efficacy of enfortumab vedotin in advanced urothelial cancer: Retrospective analysis of the Urothelial Cancer Network to Investigate Therapeutic Experiences (UNITE) Study

443 Background: Enfortumab vedotin (EV) is an antibody-drug conjugate targeting Nectin-4, which is FDA approved for patients (pts) with treatment-refractory advanced urothelial cancer (aUC). The activity of EV in pt subsets of interest such as those with distinct histological variants has not been well defined. Methods: A retrospective study of pts with aUC treated with ≥1 dose of EV as standard of care (SOC) or on a clinical trial (if trial results already reported) at 12 US sites was undertaken. Objective response rate (ORR) was investigator-assessed for pts with at least one post-baseline scan or clear evidence of clinical progression. ORR was compared across subsets of interest using proportion test. Results: A total of 184 patients with aUC were included; median age at diagnosis 70, 20% women and 60% with definitive surgery. Most common primary sites included bladder (70%) and upper tract (28%). Majority of pts (72%) had pure urothelial histology (UH) per local review, but 26% had at least a component of variant histology (VH), most commonly squamous (14%), micropapillary (8%) or plasmacytoid (3%). EV was given as monotherapy in 84% and as SOC in 58%; and 81% had ≥ 1 prior treatment in the metastatic (met) setting. ECOG PS was ≥2 in 15%; 37% had baseline neuropathy, 15% diabetes and 9% had GFR≤30. At median follow-up of 37.0 (IQR: 20.5-60.2) months from initial diagnosis, median time from met diagnosis to EV start was 11.7 (IQR: 4.3 – 20.5) months. Median duration of EV was 5.5 (IQR: 1.4 – 6.7) months, and 84% of pts were evaluable for response. ORR for evaluable pts was 53% (8% CR, 45% PR); 25% had SD and 21% PD. Median PFS and OS were not yet reached. At data cutoff in 9/2020, 55% had stopped EV (36% due to PD, 19% intolerance) and 65% were alive. Comparison of ORR in subgroups of interest for 127 evaluable pts treated with EV monotherapy is shown in the table below. Notably, among 31 pts with FGFR3 alterations, 26 were evaluable and ORR was 46%. Conclusions: In a large, retrospective, multi-institutional cohort, responses to EV were observed across a broad range of aUC pts, including pts with variant histology component, FGFR3 alterations and also in populations previously excluded from clinical trials such as pts with GFR