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 - Beyond the Abstract
High BMI was defined as >/= 30 kg/m2. These conditions are relevant given the rising incidence globally, which might influence outcomes in patients receiving checkpoint inhibitors. Patients on the JB100 trial were enrolled in the avelumab with best supportive care (BSC) arm in 350 patients and the BSC arm alone (n=350). The subgroups analyzed included high BMI in 122 patients (17.4%) and DM in 114 patients (16.3%). After a median follow-up of >/= 38 months, overall survival (OS) was shown to be 20.8 months in the avelumab arm vs 12.7 months in the BSC group, HR 0.77(CI 0.49–1.21), and progression-free survival (PFS) of 5.6 months in the avelumab subgroup compared to 2.1 months in the BSC subgroup, HR: 0.64. in the DM subgroup, avelumab showed an OS of 20.8 months compared to the BSC group at 14.5 months HR: 0.60 (CI 0.37–0.95) with progression-free survival (PFS) of 5.6 months in the avelumab subgroup compared to 2.0 months in the BSC subgroup HR: 0.5. Therefore, in these groups, avelumab plus best supportive care improved overall survival and progression-free survival compared with best supportive care alone, with outcomes generally consistent with the overall study population.
Safety findings were also comparable, with no new safety concerns identified and metabolic events reported infrequently. Grade 3 or more treatment-related adverse events occurred in about 26.9% of those with high BMI and 24.1% in those with DM, and discontinuation rates were generally low at 10.4% in those with high BMI and 9.3% in those with DM. Metabolic events reported were also quite rare, with only 1 patient having worsening of DM and occasional hyperglycemia or hypertriglyceridemia. Although the analyses were limited by their post hoc nature and small subgroup sizes, the results support avelumab maintenance as an effective and tolerable option for patients with advanced urothelial carcinoma after platinum chemotherapy, including those with common comorbidities such as high BMI or diabetes.
Avelumab first-line maintenance continues to provide meaningful survival benefits for patients with advanced urothelial carcinoma even among those with high BMI or diabetes mellitus, with no new safety concerns emerging in these subgroups. In the context of the current treatment landscape, where there are 3 level 1 evidence-based treatments for mUC, although Enfortumab vedotin and pembrolizumab are the preferred category 1 treatments, these findings support use of avelumab across a heterogeneous, comorbidity-burdened population. Therefore, avelumab first-line maintenance provides durable survival benefits and maintains a manageable safety profile in advanced urothelial carcinoma even among patients with high BMI or diabetes, reinforcing its role as a valuable treatment option after platinum chemotherapy.
Written by: Jeanny B. Aragon-Ching, MD, FACP, FASCO, Inova Schar Cancer Institute, Fairfax, VA, USA
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