Outcomes with sacituzumab govitecan (SG) in patients (pts) with advanced urothelial carcinoma (aUC) and variant histologies (VH): Analysis of the UNITE study.

• DOI: 10.1200/jco.2024.42.4_suppl.667
• Publication Date: 2024-01-29T21:06:41Z
• Authors: Amanda Nizam; Tanya Jindal; Cindy Y. Jiang; Omar Alhalabi; Matthew P. Davidsohn; Dimitra Rafailia ...; Rafee Talukder; Charles B Nguyen; Eugene Oh; Amy K Taylor; Mehmet Asim Bilen; Arnab Basu; Deepak Kilari; Hamid Emamekhoo; Shilpa Gupta; Petros Grivas; Joaquim Bellmunt; Matthew T Campbell; Ajjai Shivaram Alva; Vadim S Koshkin

667 Background: SG is approved in pts with aUC refractory to platinum-based chemotherapy (PBT) and checkpoint inhibitor therapy (CPI). Data on SG outcomes in pts with subtype/variant histologies (VH) are limited. We examined SG-treated pts in the UNITE study and hypothesized that outcomes would be similar between pts with pure urothelial histology (pUC) and any VH component. Methods: UNITE is a multi-site retrospective study of pts with aUC treated (Tx) with targeted agents, such as enfortumab vedotin (EV) and SG. Pts who received SG monotherapy were included in this analysis. Observed response rate (ORR) was assessed by investigators at each site for evaluable pts with scans after ≥ 1 SG cycle using χ2 and logistic regression. Progression-free and overall survival (PFS, OS) from SG start were assessed using KM method and Cox proportional hazards model. Results: Among 633 total pts in UNITE, 116 received SG monotherapy at 11 US sites. Median age was 70; 79 (68%) male; 97 (84%) Caucasian; 86 (74%) ECOG PS 0/1; 84 (72%) lower tract tumor; 90 (78%) visceral or bone mets; 48 (41%) Bellmunt score ≥2; 72 pts (62%) had pUC and 44 (38%) VH, including 33 (28%) with UC predominant (<50% VH) and 11 (9%) with variant predominant (≥50% VH). For prior therapy, 109 pts (94%) received >2 prior lines; 75 (65%) PBT; 102 (88%) CPI; 109 (94%) EV. Median time from metastatic diagnosis to SG start was 18.6 months (mo) (0.9-84.5). Median follow up from SG start was 10.6 mo (8.5-15.4). Median time on SG was 1.6 mo (0.2-14.7). ORR to SG was 24% (20/84); median PFS and OS from SG start were 3.7 mo (95% CI 3.0-4.6) and 6.7 mo (95% CI 5.3-10.8). VH (n ≥1) included: squamous (SQH) (19, 16%), micropapillary (9, 8%), plasmacytoid (8, 7%), adenocarcinoma (3, 3%), neuroendocrine (NE) (2, 2%). In evaluable pts with VH, ORRs: squamous (3/14), micropapillary (1/4), plasmacytoid (0/6), adenocarcinoma (2/3), NE (1/2). No significant differences were observed in outcomes between pUC and any VH or pUC and SQH (Table). Conclusions: Pts with aUC treated with SG appear to have similar clinical outcomes between pUC and any VH. Responses to SG are observed across different VH. Limitations include low power, tumor heterogeneity, lack of central pathology/scan review, selection and confounding biases. These hypothesis-generating findings suggest activity of SG post-PBT, CPI, and EV in pts with VH, but should be validated in larger cohorts with adequate sample size of specific VH and longer follow up. [Table: see text]