Ballouz, Tara

643 Background: The FDA approval of enfortumab (EV) and pembrolizumab (Pembro) combination therapy as a first-line treatment for cisplatin-ineligible patients with locally advanced/metastatic urothelial carcinoma (la/mUC) was based on the EV-103 trial. We aim to assess the clinical response rate of this combination therapy in our institution's patients with locally advanced and metastatic UC. Methods: This retrospective cohort study included 20 patients diagnosed with locally advanced/metastatic UC(la/mUC) who were treated with EV-Pembro combination for at least 2 cycles, from June 2022 to August 2023 at the Mayo Clinic. Patients who were treatment naïve or who progressed one or more lines of therapy were included in the study cohort. Main outcome of interest included imaging-based best overall response rate in terms of complete (CR) and partial (PR) response, stable disease (SD), and progressive disease (PD). Results: Out of 20 patients, the number of males and females were 16 (80%) and 4 (20%) respectively; the median age was 77 years (IQR: 51-92). 3 (15%) of patients had involvement of upper urinary tract disease along with bladder cancer. The common sites of visceral metastasis at the time of initial presentation include liver 2(10%), lung 6(30%) and lymph nodes12(60%). Common toxicities of this regimen included rash, pruritis, peripheral neuropathy, fatigue, transaminitis, dysgeusia, and diarrhea. The treatment was stopped in 10 (50%) patients due to completion of planned therapy (achieved CR or proceeded with resection of residual disease) (30%), 5 patients due to progression (50%), 1 patient due to therapy side effects (10%) and in 1 patient due to death (10%). The objective response was 45% (N =9); 5 (25%) had PR, and 4 (20%) had CR. A total of 2 (10%) had SD while 2 (10%) experienced PD. Histological correlation with clinical benefit is shown in the table. Conclusions: EV-Pembro combination therapy shows promising responses in patients who have progressed after previous lines of therapy, consistent with previously published data on EV 201 in small cohorts. However, ongoing expansion of this cohort and data from larger studies will help further elucidate survival benefits and their correlation with genetic testing. [Table: see text]

639 Background: Immunotherapy combined with chemotherapy (IO/C) as the first-line management of locally advanced or metastatic urothelial carcinoma (LA/mUC) has been investigated in multiple trials with conflicting outcomes. Therefore, we conducted a meta-analysis of available trials to compare objective response rates (ORR) of this combination regimen, both in overall and in cisplatin-ineligible populations. Methods: EMABSE and MEDLINE were searched from 2000 through July 20th, 2023, to identify phase II and III clinical trials assessing IO, C or both in LA/mUC. Main outcome of interest was objective response rates (ORR) as defined in the included trials. An inverse variance random-effects meta-analysis was performed to estimate pooled ORR using the restricted maximum likelihood estimation method. Subgroup differences were assessed among IO/C, IO alone, and C alone. The threshold for statistical significance was established at 0.1. Results: Of 5975 citations identified, a total of 26 trials with a total of 4,628 participants were included in this systematic review. In the overall group, the ORR in IO/C trials (5 trials, 1,236 patients) was 44.70% (95% CI: 21.88%- 70.0%). In IO trials (7 trials, 2,189 patients), ORR was 23.68% (19.55%- 28.36%) and in C trials (26 trials, 4,628 patients) was 43.46% (37.43%-49.68%]). In the cisplatin-ineligible group, the ORR in IO/C trials (2 trials, 240 patients) was 60.06% (33.38%-81.86%), in IO trials (6 trials, 1,103 patients) was 26.15% (23.01%; 29.56%), and in C trials (8 trials, 767 patients) was 42.45% (35.67%-49.52%). In terms of subgroup differences, the difference in ORR was statistically significant between IO/C and IO trials (p= 0.0844) and between IO and chemotherapy trials (p< 0.0001) in the overall population. Similarly, we found a statistically significant difference in ORR between IO/C and IO (p= 0.0108) and between IO and chemotherapy trials (p< 0.0001) in the cisplatin-ineligible population. No statistically significant differences were observed between IO/C and C alone. Conclusions: First-line IO/C may achieve a better objective response compared to IO alone in patients diagnosed with locally advanced/metastatic UC. Although, there appears to be a trend of greater benefit with IO/C compared to C alone, the difference was not statistically significant. The results will be updated as soon data from new trials (CheckMate 901 and EV 302) becomes available which could offer new insights. [Table: see text]

627 Background: Enfortumab vedotin (EV) is an antibody-drug conjugate recently approved to treat locally advanced or metastatic bladder cancer (la/mUC). Initial trials have shown promising response to EV in advanced urothelial cancers (UC), where prognosis is currently poor. Here, we report real-world experience using EV at a tertiary center. Methods: This study reports treatment details and outcomes in 92 patients (pts) that received at least one complete cycle of EV monotherapy in treatment of la/mUC. Treatment details include intent of cycle duration, 21 days (treatment on days 1 and 8) or 28 days (treatment on days 1, 8 and 15), dose reductions, and median number of cycles completed. Interruptions in treatment are reported as intentional (i.e. holding EV after achieving positive response) or unintentional (i.e. secondary to drug toxicity or other delay). Image-based best clinical response consists of progressive disease (PD), stable (SD), partial (PR), complete response (CR), and not evaluable (NE). Clinical benefit rate (CBR) is defined as either SD, PR, and CR outcomes. The Kaplan-Meier method was used to estimate overall survival (OS) and progression-free survival (PFS). Results: Patients mean age was 71.1 years (IQR: 66.8 - 78), 72 (79.2%) are male and 20 (20.8%) female, 89 (96.7%) pts received EV in the setting of metastatic UC, 3 (3.3%) in locally advanced UC. 13 (13.5%) pts were previously chemotherapy exposed, 9 (9.8%) were immunotherapy exposed, 60 (65.2%) were both chemo and immunotherapy exposed, and 11 (12.0%) received EV first line. 46 (50%) pts underwent 21-day treatment cycles, and 46 underwent 28-day treatment cycles. The median number of EV cycles was 3 (range 1-16) in the overall cohort, 3 in the 21-day cycle group, and 4 in the 28-day cycle group. 50 (54.3%) pts required dose reductions secondary to toxicity. 11 (12.0%) pts had planned interruptions, and 33 (35.9%) had unplanned interruptions. Best clinical response consisted of 24 (26.0%) pts with PD, 12 (13.0%) with SD, 25 (27.2%) with PR, 17 (18.5%) with CR, and 14 (15.2%) NE. CBR was 54 (58.7%) in the overall sample. CBR in the 21-day and 28-day cycle groups was identical at 27 (29.3%). EV therapy was discontinued most for cancer progression (34, 37.0%), therapy toxicity (18, 19.6%), and pt death (12, 13.0%). In 13 (14.1%) pts therapy is still ongoing. 73 (76.0%) pts had mild to moderate toxicities, and 19 (19.7%) reported severe toxicities that required hospitalization. Median OS in the total cohort was 11.01 months (95% CI: 8.51-14.6). Median PFS is 5.49 months (95% CI: 4.60-8.19). Conclusions: Real-world utilization of EV showed significant heterogeneity in administration patterns (21 days vs 28 days) and across a range of settings (first line, chemo exposed, IO exposed, chemo and IO exposed). Although EV has high response rates, more than 3/4th of patients suffered mild to moderate toxicities and 1/5th required hospitalization.