Avelumab first-line maintenance for advanced urothelial carcinoma: long-term outcomes from the JAVELIN Bladder 100 trial in older patients

Background: In the JAVELIN Bladder 100 phase III trial, avelumab first-line (1L) maintenance plus best supportive care (BSC) significantly prolonged overall survival (OS) versus BSC alone in patients with locally advanced or metastatic urothelial carcinoma (la/mUC) without progression following platinum-based chemotherapy. Older age (≥65 years) is a known risk factor for bladder cancer with a median age at diagnosis of 73.0 years. We report exploratory analyses in subgroups based on older age (≥65 years). Materials and methods: Eligible patients with la/mUC without progression after 1L platinum-based chemotherapy were randomized to receive avelumab plus BSC (n = 350) or BSC alone (n = 350). This exploratory analysis included subgroups aged ≥65 years, ≥65-<75 years, ≥75 years, and the subset aged ≥80 years. OS (primary endpoint) and progression-free survival (PFS) from randomization were analyzed using the Kaplan–Meier method. Results: Of 700 patients, 464 (66.3%) were aged ≥65 years. Median OS with avelumab plus BSC versus BSC alone was 26.1 versus 15.5 months (hazard ratio 0.70, 95% confidence interval 0.56-0.89) in all patients aged ≥65 years and 28.7 versus 17.1, 24.0 versus 13.5, and 24.9 versus 10.0 months, respectively, in patients aged ≥65-<75, ≥75, and ≥80 years. PFS analyses favored avelumab plus BSC versus BSC alone in all subgroups. No new safety concerns were identified in patients aged ≥65 years, including those treated for ≥12 months. Quality-adjusted time without symptoms or toxicity was 4.57 months longer with avelumab plus BSC versus BSC alone (a 30.35% relative improvement). Limitations include small sample size for the ≥80-year age subgroup and the exploratory design. Conclusions: These exploratory analyses support the efficacy and tolerability of avelumab 1L maintenance in patients aged ≥65 years with la/mUC that has not progressed following chemotherapy, suggesting that older age should not solely prevent a patient from receiving avelumab 1L maintenance.