Avelumab First-line Maintenance for Advanced Urothelial Carcinoma: Analysis from JAVELIN Bladder 100 by Duration of First-line Chemotherapy and Interval Before Maintenance

Background: In the JAVELIN Bladder 100 phase 3 trial, avelumab first-line maintenance + best supportive care (BSC) prolonged overall survival (OS) and progression-free survival (PFS) versus BSC alone in patients with advanced urothelial carcinoma (advanced UC) without progression after first-line platinum-based chemotherapy. Objective: To report post hoc analyses of subgroups defined by the duration of first-line chemotherapy and interval before maintenance. Design, setting, and participants: Patients with advanced UC without progression after four to six cycles of platinum-based chemotherapy and a 4–10-wk interval after chemotherapy (n = 700) were randomized to receive avelumab + BSC or BSC alone. Subgroups were defined by duration (quartile [Q]) and estimated number of cycles of chemotherapy, and interval between chemotherapy and maintenance. The median follow-up was >19 mo in both arms. Outcome measurements and statistical analysis: OS (primary endpoint), PFS, and safety were assessed. Results and limitations: Hazard ratios (95% confidence interval) for OS with avelumab + BSC versus BSC alone were as follows: by chemotherapy duration—<Q1: 0.65 (0.42–1.02), Q1–Q2: 0.79 (0.50–1.27), Q2–Q3: 0.74 (0.50–1.10), and >Q3: 0.63 (0.39–1.00); by number of cycles—four cycles: 0.69 (0.48–1.00), five cycles: 0.98 (0.57–1.71), and six cycles: 0.66 (0.47–0.92); and by interval—4–<6 wk: 0.75 (0.54–1.04), 6–<8 wk: 0.67 (0.43–1.06), and 8–10 wk: 0.69 (0.47–1.02). Results were similar for PFS. Safety was similar across subgroups. All analyses were exploratory. Conclusions: Post hoc analyses of OS and PFS in subgroups defined by first-line chemotherapy duration and interval before maintenance were generally consistent with the results in the overall population, with similar safety findings. Prospective trials are warranted to confirm these findings. Patient summary: Avelumab maintenance treatment helped patients with advanced urothelial cancer without disease progression after at least four cycles of prior chemotherapy, and who started maintenance treatment at least 4 wk after chemotherapy, to live longer.