Treatment, tolerability and outcomes of enfortumab vedotin plus pembrolizumab in advanced urothelial carcinoma: An analysis of the Austrian enfortumab registry.
Authors: Niedersuess -Beke Dora , Pichler Renate , Krauter Johanna , Luger Ferdinand , Vais Dominik , Taedcke Roman , Aufderklamm Stefan , Stoiber Franz , Shariat Shahrokh F. , Schnabel Susanne , Gampenrieder Simon Peter , Muehlmann Josef , Spiegelberg Jasmin , Bauernhofer Thomas , Banner Andreas , Weibrecht Sabine , Wiesinger Clemens , Miechowiecki Jan , Heintel Daniel , Mayrhofer Karl 
Published: February 2025

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Background:
The treatment of advanced urothelial carcinoma (UC) has dramatically changed with the introduction of antibody-drug conjugates and immunotherapy. Since the report of the EV-302 trial data in October 2023, enfortumab vedotin (EV) in combination with pembrolizumab (P) is the preferred standard of care in 1
st
line therapy.
Methods:
Clinical data were derived from 17 clinics participating in the Austrian EV registry. Patients receiving 1
st
line EV + P for advanced UC from 09/2023 to 09/2024 were included. The main objectives of the registry were to evaluate patient characteristics, including comorbidities, treatment duration, efficacy and safety in a real-world setting.
Results:
In total 103 patients were included, 24 females and 79 males with a median age of 71 years (range 32 - 92). The majority of patients (89.3%) had an eastern cooperative oncology group performance status (ECOG PS) of 0 to 1, 6.7 % patients had an ECOG PS of 2 and 3.8% had an ECOG PS of 3. Liver metastasis was present in 19.4% of patients. At the time of data cut-off, 81.6% of patients were alive. Therapy with either EV or P was ongoing in 67.0% of patients. First response evaluation was performed in 88 patients, of these the objective response rate (ORR) was 65.9% with 12.5% complete remissions. After a median follow up of 4.0 months, the median overall survival (OS) and progression free survival (PFS) was not reached. Adverse events occurred in 69.9% of patients, with ≥ grade 3 toxicities in 30.1% of patients. Therapy with either EV or P was discontinued due to toxicity in 20.4% of patients. Patients with a high (≥5) Charlson comorbidity index (CCI) had significantly worse outcomes in terms of ORR (p = 0.02), PFS (p = 0.02) and OS (p = 0.04) as compared to patients with a lower CCI (0-4). There was also a trend for more severe adverse events in patients with a high CCI (p = 0.07), however, the overall adverse event rate, dose reductions and treatment discontinuations were similar in both groups. Renal function, body mass index and known diabetes mellitus had no influence on efficacy or tolerability in our analysis. In patients with ECOG PS 2 the ORR was 71.4% which is numerically similar to patients with ECOG PS 0-1.
Conclusions:
These first Austrian real-world data evaluate the efficacy and tolerability of EV plus P in routine clinical practice. Our data confirm the ORR to the pivotal EV-302 phase III trial, however patients with significant comorbidities as reflected by a higher score in the CCI had significantly worse outcomes. Updated data with longer follow up will be presented at the meeting.