Oncology News Central (ONC)“More Treatment Is Not Always Better”: Lower EV Dose May Curb Toxicity in Older Patients with Bladder Cancer

⚠️ Retrospective / Real-World Evidence

Enfortumab vedotin (EV) has become an important treatment option in advanced urothelial carcinoma, but toxicity remains a significant concern, particularly among older adults who are often underrepresented in clinical trials. Investigators evaluated age-related toxicity and outcomes in the multicenter EVOLUTE study, which included 99 patients with advanced or metastatic urothelial carcinoma treated with EV monotherapy across seven centers in France.

Clinical Considerations

• Patients aged 70 years or older experienced significantly higher rates of grade 3 or greater toxicity than younger patients (44.2% vs 21.3%).
• Older age was the only independent predictor of severe toxicity in multivariable analysis (OR 2.63; 95% CI 1.05–6.58).
• Treatment discontinuation due to toxicity occurred in 34.6% of older patients compared with 4.3% of younger patients.
• Peripheral sensory neuropathy was the most common severe adverse event.
• Despite greater toxicity, efficacy appeared comparable. Median progression-free survival was 6.3 months in older patients versus 3.1 months in younger patients, while median overall survival was 11.6 versus 10.2 months, respectively.
• Among 12 patients who initiated therapy below the standard 1.25 mg/kg starting dose, no grade 3 or higher toxicity was observed, although the sample size was small.

Practice Applications

• Recognize older age as a potential marker for increased EV-related toxicity even when treatment efficacy appears preserved.
• Consider baseline comorbidities, performance status, neuropathy risk, and treatment goals when counseling older patients regarding EV therapy.
• Interpret upfront dose-reduction findings cautiously because the study was retrospective and involved only a small subset of patients receiving reduced-dose therapy.
• Monitor prospective investigations evaluating whether lower starting doses can maintain efficacy while improving tolerability in frail or high-risk populations.