Upfront reduced-dose EV feasible in urothelial cancer
- 19-11-2025
- Urothelial Cancer
- Editor's Choice
- News
medwireNews: Real-world data from people with advanced urothelial cancer show that upfront dose reduction of enfortumab vedotin (EV) significantly lowers the likelihood of treatment interruption without adversely affecting overall survival (OS).
“These findings align with studies from other tumor types and drug classes that dose reduction may improve treatment tolerability in older patients without detrimental effects on survival outcomes,” say the investigators in a research letter to JAMA Oncology.
“Future pragmatic trials could investigate whether titrated EV dosing can optimize tolerability and quality of life while maintaining efficacy.”
Giving the background to the research, the authors explain that EV plus pembrolizumab “is now the preferred first-line therapy for advanced urothelial cancer, yet little is known about the impact of EV dose reduction on treatment continuity or survival.”
They highlight that “[d]ose reduction is common in routine care,” and therefore “[t]his knowledge gap poses a challenge to clinicians who must weigh the risks and benefits of dose reduction, particularly in physiologically vulnerable adults.”
The team collated data from the US-based Flatiron Health Research Database on 496 patients with advanced urothelial cancer who initiated first-line EV plus pembrolizumab between April 2023 and December 2024.
A total of 23.6% of the patients received upfront reduced-dose EV, defined as a dose of 1.00 or 0.75 mg/kg for either of the first two doses, while the remaining 76.4% received standard dosing at 1.25 mg/kg for both.
The median age of the reduced- and standard-dose participants was 78 and 72 years, respectively, and the majority in both groups were men, at a respective 72.6% and 77.0%.
After inverse probability of treatment weighting to account for baseline differences, the risk for EV interruption – defined as the time from treatment initiation to the first gap of at least 35 days between consecutive EV doses – was halved among patients who received the reduced versus standard dose upfront, at a significant hazard ratio (HR) of 0.49.
However, there was no significant difference in OS between the reduced- and standard-dose groups, with a nonsignificant adjusted HR of 1.24, report Ryan Chow and colleagues from the University of Pennsylvania in Philadelphia, USA.
The researchers acknowledge limitations of the analysis, such as “the possibility of unmeasured or residual confounding, including the lack of data on sites of metastases and disease burden.”
They continue: “Follow-up time was limited due to the recent approval of [first-line] EV plus pembrolizumab, highlighting the need for larger cohorts with longer observation.”
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