Avelumab first-line maintenance for advanced urothelial carcinoma: long-term outcomes from the JAVELIN Bladder 100 trial in patients with high body mass index or diabetes mellitus

Background: Avelumab first-line maintenance is the recommended treatment option for patients with advanced urothelial carcinoma (UC) without progression following platinum-based chemotherapy (PBC), based on the phase III JAVELIN Bladder 100 trial. High body mass index (BMI; ≥30 kg/m²) and diabetes mellitus (DM) are risk factors for bladder cancer. We report exploratory analyses from JAVELIN Bladder 100 in patients with high BMI or documented controlled DM at the time of random assignment. Patients and methods: JAVELIN Bladder 100 enrolled patients with advanced UC without progression after first-line PBC, who were randomly assigned to receive avelumab plus best supportive care (BSC; n = 350) or BSC alone (n = 350). The primary endpoint was overall survival (OS) from the time of random assignment. Results: Overall, 122 patients (17.4%) had high BMI and 114 (16.3%) had DM. After a median follow-up of ≥38 months in both arms, hazard ratios for OS with avelumab plus BSC versus BSC alone were 0.77 [95% confidence interval (CI) 0.49-1.21] in patients with high BMI and 0.60 (95% CI, 0.37-0.95) in patients with DM. Long-term safety of avelumab maintenance in these subgroups was generally consistent with that of the overall population. Conclusions: Exploratory analyses support the use of avelumab first-line maintenance in patients with advanced UC without progression following PBC, including those with high BMI or DM.