Avelumab Maintenance Therapy in Advanced Urothelial Carcinoma: Implications of Timing and Treatment Sequencing

Background: Platinum-based chemotherapy (PBC) followed by avelumab maintenance is a treatment option for patients with advanced urothelial carcinoma (aUC) patients. However, the optimal treatment sequencing in the era of antibody–drug conjugates (ADCs) is yet to be determined. Recent studies suggest that the timing of immune checkpoint inhibitor (ICI) administration may impact patient outcomes, with a potential benefit from morning infusions. Methods: This retrospective study included 105 patients with aUC treated with avelumab in Portugal and intended to assess the safety and clinical outcomes (progression-free survival (PFS), overall survival (OS), and overall response rate (ORR)) and evaluate the impact of treatment timing (morning vs. afternoon) on patient outcomes. Results: The median follow-up from the start of avelumab was 17.7 months, the median PFS (mPFS) was 9.8 months (95% CI 4.9–14.7), and the median OS (mOS) was 39.5 months (95% CI 13.2–65.7). Immune-related adverse events (irAEs) were reported in 65.8% of patients, with 6.7% experiencing G3 irAEs. Among those who received a subsequent-line ADC upon disease progression (43%), the mOS from the start of avelumab was 23.1 months (95% CI 9.2–37.0). Multivariate analysis showed significant improvement in mOS with morning avelumab infusions (HR 0.35, 95% CI: 0.12–0.97, p = 0.042) and a trend towards improved mPFS (HR 0.43, 95% CI: 0.179–1.02, p = 0.055). Conclusions: This study confirms the clinical efficacy and safety of avelumab, showing improved outcomes over JAVELIN Bladder 100 and suggesting that morning infusions may offer a survival benefit in this context. Further research is needed to optimize treatment sequencing and explore the impact of infusion timing in ICI strategies.