Outcomes with subsequent therapies post-enfortumab vedotin/pembrolizumab (EVP) in patients (pts) with advanced urothelial carcinoma (aUC): Analysis of the UNITE study.

Abstract

705 Background: EVP is now the preferred first line (1L) treatment (tx) for aUC. However, outcomes with subsequent therapies are not well defined and require evaluation. Methods: We included pts from UNITE, a multi-institutional retrospective aUC cohort, who received ≥1 cycle of 1L EVP followed by second line (2L) tx. Median progression free survival (mPFS) and overall survival (mOS) from EVP and 2L tx start were estimated using Kaplan Meier (KM) method. Median follow up (mf/u) time from EVP and 2L tx start were calculated using reverse KM. Overall response rate (ORR) was investigator assessed. Odds of response and survival to each 2L tx were compared to platinum-based chemotherapy (PB CTx) using univariable logistic regression. Results: Among 377 EVP 1L pts: 114 (30%) are still on tx, 58 (15%) progressed without 2L tx, 23 (6%) went to hospice/passed, 18 (5%) tx break/surveillance, 60 (16%) stopped due to intolerance, 17 (5%) other (lost to f/u, local consolidation, insurance delay), and 20 (5%) had unknown EVP tx status; 68 (18%) received 2L tx: 26 PB CTx (39%) 14 (21%) sacituzumab govitecan (SG), 7 (10%) erdafitinib (erda), 6 (9%) trastuzumab deruxtecan (T-DXd), 2 (3%) taxane-based (TB) CTx, 5 (7%) clinical trial, 7 (10%) radiation (RT), 1 unknown. We excluded PB CTx + immunotherapy (n = 2), clinical trial pts, RT, and unknown tx. Among 53 evaluable pts, median age was 72 (range 56-97), majority were male (83%), White (93%), had primary bladder tumor (69%), pure urothelial histology (58%), and ECOG PS < 1 (83%). Mf/u time from EVP start was 18 months (mos) (95% CI 14.5-20.5). ORR to 1L EVP was 45% (3 CR, 21 PR) and mPFS was 5.5 mos (95% CI 4.4-7.1). Mf/u time from 2L tx start was 10 mos (95% CI 5.8-13.4). 34 pts were evaluable for 2L ORR; 24% responded (2 CR, 6 PR). Both CRs and 3 PRs occurred with PB CTx; 1 PR occurred with SG, T-DXd, and erda. Across 2L tx: mPFS was 2.8 mos (95% CI 1.8-6.2) and mOS 9.0 mos (95% CI 6.0-NR) with 57% (n = 30) alive at last f/u. No clear association was seen between 2L tx and OS (p = 0.52), PFS (p = 0.14), or ORR (Table). Conclusions: We observed modest ORR and survival with 2L tx in the post-EVP setting for pts with aUC, highlighting the need for additional therapies. Results may inform prognostic estimates and help guide the design of post-EVP trials. Larger cohorts are required to validate these findings. 2L Tx ORR: tx vs PB CTx, OR (95% CI) mPFS, mo (95% CI) PFS: tx vs PB CTx, OR (95% CI) mOS, mo (95% CI) OS: tx vs PB CTx, OR (95% CI) PB CTx (N=24) 4.1 (1.8-NR) NR (6.0-NR) SG (N=14) 0.29 (0.03-3.0, p=0.30) 2.8 (1.8-NR) 1.1 (0.4-2.8, p=0.87) 6.7 (3.6-NR) 1.6 (0.6-4.5, p=0.34) Erda (N=7) 0.5 (0.04-5.7, p=0.58) 1.6 (0.9-NR) 1.4 (0.4-4.3, p=0.59) 2.1 (1.8-NR) 1.8 (0.5-6.8, p=0.39) T-DXd (N=6) 0.5 (0.04-5.7, p=0.58) 5.8 (2.5-NR) 0.8 (0.3-2.5, p=0.70) 8.5 (3.4-NR) 1.4 (0.4-5.4, p=0.60) TB CTx (N=2) 0 (0-inf, p=0.99) 0.7 (0.0-NR) 6.5 (1.4-31.2, p=0.02) NR (NR-NR) 0 (0-inf, p=1.00)