Tripathi, Abhishek

4584 Background: EVP is the preferred frontline regimen in pts with aUC. Despite initial response to treatment, many pts treated with EVP ultimately have progression. We hypothesized that recurrence patterns would differ between pts with and without baseline liver metastases. Methods: UNITE is a multi-institutional retrospective database capturing clinical and treatment characteristics of pts with aUC receiving systemic therapies. We queried this database to identify pts who achieved an observed response (OR) to EVP. Pts were grouped by initial metastatic sites using a non-mutually exclusive approach. Descriptive statistics were used to summarize observed response rates (ORR) and recurrence patterns at time of progression. Progression-free survival (PFS) from start of EVP was estimated using the Kaplan-Meier method. The effect of liver metastases on PFS was assessed via multivariable Cox regression. Median-follow up time was estimated using the reverse Kaplan-Meier method. Statistical analyses were conducted in RStudio. Results: We identified 464 pts treated with EVP (median age 72; 74% male, 80% White). Best ORR in pts with baseline liver metastases (n=77) were complete response 9%, partial response 35%, stable disease 18%, and progressive disease 21%, compared with 18%, 37%, 27%, and 18%, respectively, in pts without baseline liver metastases (n=325). The estimated median follow-up time was 52 weeks (95% CI 48-62). Among pts with initial OR to EVP, those with baseline liver metastases showed a non-significant trend toward shorter PFS (HR 1.35; 95% CI 0.67–2.75; p=0.40) versus those without baseline liver metastases. Among pts with initial OR to EVP and subsequent progression the distribution of sites of recurrences at progression for those with (n = 10) and without (n = 40) baseline liver metastases were: liver (50% vs. 10%), lymph nodes (60% vs. 55%), lungs (50% vs. 38%), bone (20% vs 20%), and primary tumor (20% vs 25%). EVP responders with baseline liver metastases had a numerically higher rate of site-specific metastasis resolution at progression versus those with lymph node or lung metastases (Table). Conclusions: Our analysis suggests that liver metastases may be associated with shorter PFS among EVP responders, though these pts frequently do not retain liver metastases at time of progression. Study limitations include retrospective analysis, investigator-assessed response, small sample size, selection and confounding biases. Patterns of recurrence following EVP merits further evaluation. Metastatic Site Pts with Site-Specific Baseline Metastases (n) Pts with Resolution of Site-Specific Metastases at Progression, n (%) Pts without Baseline Metastases at Site (n) Pts who Remained Free of Site-Specific Metastases at Progression, n (%) Liver 10 5 (50%) 40 36 (90%) Lymph Nodes 37 12 (32%) 13 10 (77%) Lungs 26 8 (31%) 24 22 (92%)

4565 Background: EVP is the preferred 1 st -line regimen for patients (pts) with aUC. EV-related toxicities are often managed with dose adjustments, such as reductions and holds. Analysis of EV monotherapy trials showed consistent survival outcomes despite dose adjustments. We hypothesized that on-treatment EV dose adjustments would not impact survival in these pts. Methods: Pts with aUC treated with EVP in the multisite UNITE study were analyzed. Early dose reductions (DR) and holds were defined as occurring < 9 weeks from EVP start, with the remainder classified as late. Pts with DR at treatment start were excluded. Survival endpoints were progression-free survival (PFS) and overall survival (OS) from EVP start, assessed by Kaplan-Meier analysis and Cox models. Multivariable Cox analysis (MVA) included age (≥ 75 vs < 75), ECOG performance status (0-1 vs 2-3), Hgb level (< 10 vs ≥ 10) and liver metastases (present vs not). A time-dependent covariate was used to reduce immortal time bias. Complementary MVA landmark analyses were performed, aligned to the total number of treatment cycles received, with six analyses from cycles 2 to 7. Results: 360 pts from 17 sites were included (median age 70; 78% Caucasian; 76% male; 27% upper tract primary; 35% histology subtype component; 17% with liver metastasis; 78% frontline); median follow-up was 11.7 months (95% CI [10.79, 13.08]). Median number of cycles was 6 in pts with DR and 3 with no DR. Early DRs (100 pts [28%]) and holds (18 pts [5%]) were most commonly due to rash (28% of all early DRs and holds). Late DR (75 pts [21%]) and holds (50 pts [14%]) were most commonly due to neuropathy (52% of all late DRs and holds). Pts with early or late DR had longer PFS and OS vs those who did not (Table); however, there was no significant PFS or OS difference with dose hold vs no hold (PFS HR 0.65, 95%CI (0.40, 1.05), p = 0.08; OS HR 0.70, 95%CI (0.39, 1.27), p=0.24). In landmark analyses, about 50% of pts had DR; no significant difference in PFS or OS was observed at most landmarks, except for longer OS in the DR cohort at cycle 4 (HR 0.53, 95% CI (0.29, 0.98), p = 0.042) and cycle 5 (HR 0.43, 95% CI (0.19, 0.99), p = 0.048). Conclusions: In this real-world retrospective analysis, EVP efficacy was maintained despite DR and dose holds. Survival difference noted in the time-dependent analyses were not consistently reproduced in landmark analyses, suggesting exposure-related selection bias rather than causal effect. Prospective studies are warranted to validate these hypothesis-generating findings. Association of EV DR with PFS/OS (time-dependent analyses). Early DR Late DR DR vs no DR outcomes UVAHR (95% CI), p MVAHR (95% CI), p UVAHR (95% CI), p MVAHR (95% CI), p PFS 0.50 (0.35, 0.72), <.001 0.56 (0.38, 0.84), 0.005 0.32 (0.21, 0.49), <.001 0.36 (0.23, 0.57), <.001 OS 0.51 (0.32, 0.79), 0.003 0.57 (0.35, 0.92), 0.022 0.26 (0.15, 0.45), <.001 0.31 (0.17, 0.55), <.001