The first real-world evidence on dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin followed by switch maintenance avelumab in advanced urothelial carcinoma: a propensity score-matched study

TL;DR

This study shows that using dd-MVAC followed by avelumab improves survival in patients with advanced urothelial carcinoma.

Contribution

First real-world evidence of dd-MVAC followed by avelumab in advanced urothelial carcinoma.

Findings

Median overall survival was 24 months and progression-free survival was 7 months.

Patients receiving avelumab had significantly longer survival compared to those who did not.

dd-MVAC followed by avelumab remains a valid treatment option in the new treatment landscape.

Abstract

Dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (dd-MVAC) is an established regimen for advanced urothelial carcinoma (aUC). Although platinum-based chemotherapy, typically gemcitabine and cisplatin, followed by switch maintenance avelumab has been a recommended strategy for aUC, no study has evaluated outcomes of dd-MVAC followed by avelumab therapy.

We reviewed 71 patients treated with first-line dd-MVAC for aUC at two university hospitals between 2018 and 2024. Overall survival (OS) and progression-free survival (PFS) were assessed as endpoints. Additionally, among patients who achieved ≥ stable disease, we performed propensity score matching between patients with and without avelumab to balance their background characteristics.

Of 71 patients, 49 (69%) experienced disease progression and 30 (42%) died during the median follow-up of 13 months. Median OS and PFS were 24 and 7 months, respectively. Among 59 patients who achieved ≥ stable disease after completion of dd-MVAC, 35 received switch maintenance avelumab, while the remaining 24 did not. After propensity score matching, patients with avelumab had significantly longer OS and PFS (both: not reached) than those without (OS: 28 months; PFS: 7 months).

We herein report outcomes of dd-MVAC followed by switch maintenance avelumab in real-world patients with aUC for the first time. Avelumab therapy was significantly associated with longer survival in patients who achieved ≥ stable disease after first-line dd-MVAC. Given the excellent survival outcomes, dd-MVAC followed by switch maintenance avelumab may still be a valid option for aUC even in the new treatment paradigm as typified by enfortumab vedotin and pembrolizumab.

The online version contains supplementary material available at 10.1007/s10147-025-02729-x.

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