Clinical outcomes of frontline GemFLP in advanced urachal and non-urachal adenocarcinomas of the urinary tract: The MD Anderson Cancer Center (MDACC) experience.

Abstract

630 Background: Adenocarcinomas of the urinary tract, including urachal (UA) and non-urachal (NUA) subtypes, are rare tumors. Triplet regimens combining gemcitabine, a taxane or 5-fluorouracil (5-FU)/leucovorin (L), and cisplatin (P), have been developed. Methods: We retrospectively reviewed records of patients receiving frontline (1L)GemFLP (Gemcitabine 200 mg/m2 IV on days 1 and 5; 5-FU 200 mg/m2 IV on days 1, 2, 3, 4, 5; L 10mg/m2 IV on days 1, 2, 3, 4, 5; P 20mg/m2 IV on days 1, 2, 3, 4, 5) in advanced UA and NUA at MDACC between 2003 and 2023. Advanced disease is defined as Sheldon stages IVA/IVB in UA and TNM stage IV in NUA. Imaging-based best overall responses (BOR) were complete (CR), partial (PR), stable (SD), progressive (PD) or non-evaluable (NE). Overall response rate (ORR) covers CR + PR, while disease control rate (DCR) covers CR + PR + SD. We report overall survival (OS) and progression-free survival (PFS) from GemFLP start. Results: Baseline characteristics of UA (n=40) and NUA (n=28) are in Table. In UA, bladder dome was primary location in 39 (97.5%). NUA pts had either bladder (11, 39.3%) or urethral (17, 60.7%) origin. BOR in 1L GemFLP are shown in Table. In UA, ORR is 20% and DCR is 72.5%. Median OS (mOS) is 19.8 months (95% CI: 12.2 - 30.6) and median PFS (mPFS) is 5.3 mo (95% CI: 3.1 – 6.3). In UA, pts with CR, PR, or SD have a significantly longer mOS than pts with PD [26 mo (16.2 – 35.6) vs. 7.7 mo (2.67 – 11.9), log-rank p <0.0001]. Meanwhile, in NUA, ORR is 35.7% and DCR is 75%. mOS is 12.95 mo (95% CI: 7.1-20.2) and mPFS is 5.3 mo (1.93 – 7.6). A similar significant survival benefit is seen in NUA pts with disease control versus pts with PD [17.6 mo (12.6 – 25.9) vs. 5 mo (2.63 – 7.1), p <0.0001]. Surgical consolidation was offered for 6 UA pts (3 PR, 3 SD), 3 of whom were regional N+ only, and for 4 NUA pts (1 CR, 1 PR, 2 SD) who were all regional N+ only. All except one showed residual pathological disease. Conclusions: 1L GemFLP is an active regimen in advanced UA and NUA, with a DCR of >70%. Pts with disease control (CR, PR, or SD) have a clear survival benefit compared to non-responders. 1L GemFLP might offer chances at surgical consolidation after disease control for pts with regional node-positive only disease, with larger cohorts needed to confirm findings. [Table: see text]