Impact of squamous histology on outcomes with enfortumab vedotin in patients with advanced urothelial carcinoma: Analysis of the UNITE study.

Abstract

651 Background: Squamous histology (SH) is the most common variant of Urothelial Carcinoma (UC) and is associated with lower response rates to chemotherapy. The impact of SH on outcomes with enfortumab vedotin (EV) is less defined. We hypothesized that increased SH component would correlate with inferior outcomes with EV treatment. Methods: UNITE is a multi-institutional retrospective study in pts advanced UC (aUC) treated with targeted agents. In this analysis, we compared EV monotherapy outcomes in pts with pure UC (pUC) and pts with urothelial predominant histology (UCP) [<50% SH], SH-predominant [50-99% SH] and pure SH (pSH) [100% SH] respectively. We also compared pSH to UCP and SHP. Observed Response Rate (ORR) was compared in evaluable pts with scans after ≥1 cycle of EV using Chi-squared test. Progression-free survival (PFS) and overall survival (OS) from EV start were assessed and compared using the KM method and Cox proportional hazard test. Results: This analysis included 460 pts from 17 US sites treated with EV monotherapy. 366 pts had pUC and 94 pts had SH component (including pSH). In the overall cohort, median age was 70, 73% men, 88% Caucasian, 73% ECOG PS 0-1, 67% lower tract tumor, 30% liver mets, 38% bone mets, 65% had ≥ 2 prior therapy lines. There were no significant differences in baseline clinical characteristics between pts with pUC vs SH component except for higher incidence of liver mets in pts with pUC (32% vs 20%; p = 0.02). Among all 460 pts, median follow up was 20.7 mos from EV start, ORR was 51%, mPFS and mOS were 5.8 mos (95% CI: 5.3-6.4) and 12.7 mos (95% CI: 11.5-14.3). Among 94 pts with SH component, 70 were UCP, 17 SHP and 7 pSH. Inferior outcomes were noted in pts with pSH relative to pts with pUC and pts with UCP (Table). No differences in outcomes were seen across other cross-group comparisons. Conclusions: These hypothesis-generating findings suggest that SH component may impact outcomes with EV treatment in pts with aUC. A subset of pts with SH-predominant histology can have robust responses and outcomes with EV treatment, but larger studies and further biomarker data are needed to determine pts most likely to benefit. Patients with pSH are shown to have worse outcomes with EV, but further studies with a larger sample size are needed to validate our findings and define the role of EV for this rare and biologically distinct entity. [Table: see text]