Volume 43, Issue 10, October 2025, Pages 594.e19-594.e29Author links open overlay panel, , , , , , , , , , , , , , Highlights•

We report real-world outcomes with 1L PBC and avelumab 1LM uptake in la/mUC in the US.

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Outcomes with 1L PBC in our study align with clinical trials and real-world studies.

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Post FDA approval, avelumab 1LM uptake was high (70%) in patients deemed eligible.

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After avelumab, 40% of patients received 2L therapy, mostly with enfortumab vedotin.

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Post guideline changes, further studies are needed to optimize treatment sequencing.

AbstractBackground

A standard treatment option for patients with locally advanced/metastatic urothelial carcinoma (la/mUC) is first-line platinum-based chemotherapy (1L PBC) followed by avelumab 1L switch maintenance (1LM) in patients without progression. This study aimed to evaluate the real-world treatment patterns and outcomes in patients with la/mUC in the US treated with 1L PBC and characterize the early adoption of avelumab 1LM following FDA approval in June 2020.

Methods

This retrospective cohort study identified adults diagnosed with la/mUC between January 2017 and September 2021 using electronic health records from the Flatiron Health database. Patients were grouped based on real-world response to 1L PBC: complete or partial response (rwCR/PR) or stable disease (rwSD). Baseline characteristics and treatment patterns were described. Clinical outcomes, including real-world overall survival (rwOS) and progression-free survival (rwPFS), were analyzed using the Kaplan-Meier method.

Results

Of 1,703 identified patients with la/mUC treated with 1L PBC, 1,245 (73%) had response data available during the study period, with 998 (80%) having a best response of rwCR/PR (60%) or rwSD (20%). Demographic and clinical characteristics were similar between patients with rwCR/PR and rwSD. Patients with rwCR/PR had longer median rwOS and rwPFS from 1L PBC initiation vs patients with rwSD. Of patients evaluated after FDA approval of avelumab 1LM on June 30, 2020, 435 discontinued 1L PBC. Of these patients, 339 had response data, and 138 of those without progression were considered avelumab 1LM eligible. Of these, 97 (70%) initiated avelumab 1LM within 180 days following last administration of 1L PBC, with 40 patients receiving second-line (2L) treatment, most commonly enfortumab vedotin (60%).

Conclusion

In the post–FDA approval period, uptake of avelumab 1LM was high (70%) in patients with rwSD or rwCR/PR following 1L PBC, and 41% of these patients received 2L treatment, most commonly with enfortumab vedotin.

Keywords

Real-world outcomes

Locally advanced/metastatic urothelial carcinoma

Treatment patterns

Platinum-based chemotherapy

Avelumab first-line maintenance

Electronic health records

Treatment sequencing

Abbreviations1LM

first-line maintenance

ADC

antibody-drug conjugate

ECOG PS

Eastern Cooperative Oncology Group performance status

EHR

electronic health record

FDA

Food and Drug Administration

la/mUC

locally advanced/metastatic urothelial carcinoma

NCCN

National Comprehensive Cancer Network

PBC

platinum-based chemotherapy

rwCR

real-world complete response

rwOS

real-world overall survival

rwPFS

real-world progression-free survival

rwPR

real-world partial response

rwSD

real-world stable disease

© 2025 The Authors. Published by Elsevier Inc.