The landscape of advanced urothelial carcinoma treatment has been further clarified with new data from the phase 3 JAVELIN Bladder 100 trial, showing that first-line maintenance therapy with avelumab plus best supportive care (BSC) delivers significant survival benefits regardless of patients' diabetes status.
In a detailed analysis presented at the 2025 Genitourinary Cancers Symposium, researchers revealed compelling survival data across patient subgroups. For patients with diabetes mellitus, avelumab plus BSC achieved a median overall survival (OS) of 20.8 months compared to 14.5 months with BSC alone (HR, 0.60; 95% CI, 0.37-0.95). The survival advantage extended to non-diabetic patients, who experienced a median OS of 24.7 months with avelumab plus BSC versus 15.8 months with BSC alone (HR, 0.78; 95% CI, 0.64-0.96).
Progression-Free Survival Benefits
The progression-free survival (PFS) data reinforced the treatment's efficacy. Diabetic patients receiving avelumab maintenance showed a median PFS of 5.6 months versus 2.0 months with BSC alone. Similarly, non-diabetic patients achieved a median PFS of 5.4 months with avelumab compared to 2.1 months with BSC alone.
"These results demonstrate that avelumab frontline maintenance provides consistent long-term efficacy benefits regardless of diabetes status in patients who respond to initial platinum-based chemotherapy," stated Dr. Shilpa Gupta, director of Genitourinary Medical Oncology at the Cleveland Clinic Taussig Cancer Institute.
Patient Demographics and Treatment Characteristics
The study population reflected real-world demographics, with median ages of 70-72 years in the diabetes cohort and 68-69 years in the non-diabetes group. The majority of participants were male, with a higher proportion of PD-L1 positive patients in the avelumab treatment arms.
Notably, carboplatin-based chemotherapy regimens were more frequently used in diabetic patients during initial treatment, while response rates to first-line chemotherapy varied between groups. In the diabetes cohort, 63.6% of avelumab-treated patients achieved complete or partial response, compared to 73.9% in the non-diabetes group.
Safety and Tolerability Profile
The safety analysis revealed a manageable adverse event profile across both patient populations. Grade 3 or higher treatment-related adverse effects occurred in 24.1% of diabetic patients and 18.6% of non-diabetic patients receiving avelumab. The most common serious adverse events included elevated lipase and amylase levels, and anemia.
Immune-related adverse events were observed in approximately 32% of avelumab-treated patients in both diabetic and non-diabetic groups, with common manifestations including pruritus, hypothyroidism, and fatigue. Treatment discontinuation rates due to adverse events remained relatively low, affecting 11.1% of diabetic and 14.8% of non-diabetic patients.
Clinical Implications
These findings are particularly significant given that diabetes is a known risk factor for bladder cancer and is more prevalent in older adults. Previous concerns about reduced immunotherapy efficacy in diabetic patients have been effectively addressed by this analysis, supporting the use of avelumab maintenance therapy across patient populations.
The results further validate avelumab's position in current treatment guidelines and provide reassurance to clinicians treating advanced urothelial carcinoma patients with comorbid diabetes. The consistent efficacy and safety profile across patient subgroups reinforces the role of avelumab maintenance as a standard of care in this therapeutic setting.
