Editorial Comment to Real‐World Use of Avelumab First‐Line Maintenance for Locally Advanced or Metastatic Urothelial Carcinoma in Japan: Treatment Patterns, Effectiveness, and Safety

The therapeutic landscape for locally advanced or metastatic urothelial carcinoma (la/mUC) has evolved rapidly, with multiple first‐line (1 L) and subsequent systemic options currently available. In this context, real‐world evidence has become increasingly important for understanding how treatments perform outside the controlled environment of randomized trials. Japan is uniquely positioned in this regard, given its universal health insurance system, broad access to newly approved agents, and mandatory post‐marketing surveillance. The review by Kikuchi et al. provides a timely and comprehensive synthesis of Japanese real‐world data on 1 L maintenance avelumab, integrating findings from three complementary datasets—post‐marketing surveillance, JAVEMACS, and JAVEMACS‐D [1].

A major strength of this review is its focus on Japanese clinical practice, where patient demographics, treatment patterns, and sequencing differ meaningfully from Western countries. The authors highlight that patients receiving avelumab maintenance in Japan tend to be older and more clinically heterogeneous than those enrolled in JAVELIN Bladder 100, yet effectiveness outcomes appear comparable or even numerically favorable. The frequent use of cisplatin‐based regimens, often with transition to avelumab after three to four cycles, reflects pragmatic decision‐making in routine care and aligns with emerging evidence suggesting limited incremental benefit from extended platinum exposure.

The review also underscores the growing role of enfortumab vedotin (EV) as a second‐line therapy following 1 L maintenance avelumab. Both JAVEMACS and JAVEMACS‐D demonstrate rapid uptake of EV and suggest that the sequence of platinum‐based chemotherapy, maintenance avelumab, and EV may be associated with favorable outcomes. Although these observations are exploratory, they provide valuable insight into contemporary Japanese treatment sequencing and highlight the importance of real‐world evidence in informing clinical decisions.

The authors appropriately describe the safety profile of maintenance avelumab, with post‐marketing surveillance offering detailed characterization of infusion‐related reactions and immune‐related toxicities. The consistency of these findings with clinical trial data, despite an older population, reinforces the feasibility of delivering avelumab maintenance in routine practice when standard premedication and monitoring are applied.

With all real‐world evidence, certain limitations warrant consideration. Selection bias, immortal time bias, and the absence of centralized radiologic review may influence effectiveness estimates. Claims‐based analyses, such as JAVEMACS‐D, may have incomplete mortality capture. Although these factors do not diminish the value of the datasets, we would underscore the need for cautious interpretation and continued methodological refinement in future RWE studies.

Importantly, the review situates these findings within the broader context of shared decision‐making (SDM) [2]. As multiple first‐line strategies—including EV plus pembrolizumab and nivolumab plus gemcitabine/cisplatin—become available, clinicians must balance efficacy, toxicity, treatment burden, and patient preferences [3]. The Japanese real‐world evidence summarized here provides clinicians with realistic expectations regarding treatment trajectories and sequencing, thereby supporting more informed SDM.

Looking ahead, further real‐world evidence will be essential to clarify optimal sequencing in the era of EV‐based combinations and biomarker‐directed therapy. Prospective registries and linkage of clinical and claims data may help address current gaps. This review provides valuable guidance for Japanese clinicians navigating an increasingly complex treatment landscape by assembling a thoughtful and clinically relevant synthesis.

Author Contributions

Makito Miyake: writing – original draft, writing – review and editing.

Conflicts of Interest

The author declares no conflicts of interest.

Data Availability Statement

Data sharing not applicable to this article as no datasets were generated or analysed during the current study.