Treatment patterns and clinical outcomes with platinum-based chemotherapy after enfortumab vedotin and pembrolizumab in patients with metastatic urothelial carcinoma.

4573 Background: Enfortumab vedotin and pembrolizumab (EV/P) emerged as the new standard of care for previously untreated metastatic urothelial carcinoma (mUC), shifting the treatment paradigm. Currently, there are no guidelines for management after EV/P as the outcomes of subsequent systemic treatments, including platinum-based chemotherapy, remain unknown. Methods: Our retrospective cohort of patients with mUC treated with EV/P at Memorial Sloan Kettering Cancer Center was reviewed to identify patients receiving subsequent systemic treatments. Clinical data were collected by chart review. Response to EV/P and platinum-based chemotherapy was determined by physician assessment using RECIST v1.1. Progression free and overall survival (PFS, OS) were calculated using the Kaplan-Meier method. Results: Of 208 patients treated with EV/P between 10/2018 and 9/2024, we identified 56 patients that received any subsequent systemic treatments. In 68% of patients (n = 38), the initial post EV/P regimen administered was platinum-based chemotherapy. Other therapies included sacituzumab govitecan (n = 6), clinical trials (n = 5), trastuzumab deruxtecan (n = 4), erdafitinib (n = 2) and non-platinum chemotherapy (n = 1). In the 38 patients treated with platinum-based chemotherapy, median age was 74 years, 66% were men, 32% had upper tract primary and divergent histology/subtype component was reported in 47% of cases. One patient had prior platinum exposure (neoadjuvant treatment with rapid metastatic recurrence < 6 months). 16 patients had disease response to EV/P (observed response rate [ORR] 42%, 95% CI 27%, 59%). 36 patients (95%) received doublet therapy with gemcitabine and either cisplatin (n = 7) or carboplatin (n = 29), the two remaining patients received carboplatin/gemcitabine/paclitaxel and carboplatin/etoposide. 7 patients (18%) received maintenance avelumab following platinum. Median follow up was 5 months (IQR: 2.5-6.3). ORR was 50% (95% CI 34%, 66%), including one patient with complete response (CR; 2.9%) and 16 patients with partial response (PR; 47%). Among the patients with CR or PR, median duration of response was 3.8 months (IQR: 2.0-4.6). Median PFS was 4.4 months (95% CI 3.7, 7.8) and median OS was 12 months (95% CI 9.7, 17). Conclusions: In a real-world cohort of patients with mUC, platinum-based chemotherapy had substantial antitumor activity after EV/P, although progression-free survival and duration of response were modest. This work provides useful information to further future trial design in the post EV/P setting. Disease response with platinum-based chemotherapy after enfortumab vedotin and pembrolizumab. N=38 (%) 95% CI Observed response rate 17 (50%) 34%, 66% Complete response 1 (2.9%) 0.15%, 17% Partial response 16 (47%) 30%, 65% Stable disease 6 (18%) 7.4%, 35% Progressive disease 11 (32%) 18%, 15% Unknown 4