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.
背景：对于晚期尿路上皮癌（aUC）患者，以铂类为基础的化疗（PBC）后接续阿维鲁单抗维持治疗是一种治疗选择。然而，在抗体药物偶联物（ADC）时代，最佳的治疗序贯方案尚未确定。近期研究表明，免疫检查点抑制剂（ICI）的给药时机可能影响患者预后，晨间输注可能带来潜在获益。 方法：这项回顾性研究纳入了葡萄牙105例接受阿维鲁单抗治疗的aUC患者，旨在评估其安全性和临床结局（无进展生存期（PFS）、总生存期（OS）和总缓解率（ORR）），并评估治疗时机（晨间 vs. 下午）对患者结局的影响。 结果：从开始阿维鲁单抗治疗起的中位随访时间为17.7个月，中位PFS（mPFS）为9.8个月（95% CI 4.9–14.7），中位OS（mOS）为39.5个月（95% CI 13.2–65.7）。65.8%的患者报告了免疫相关不良事件（irAEs），其中6.7%为G3级irAEs。在疾病进展后接受后续ADC治疗的患者（43%）中，从开始阿维鲁单抗治疗起的中位OS为23.1个月（95% CI 9.2–37.0）。多变量分析显示，晨间输注阿维鲁单抗显著改善了mOS（HR 0.35，95% CI：0.12–0.97，p=0.042），并在改善mPFS方面显示出趋势（HR 0.43，95% CI：0.179–1.02，p=0.055）。 结论：本研究证实了阿维鲁单抗的临床疗效和安全性，其结局优于JAVELIN Bladder 100研究，并提示在此背景下晨间输注可能带来生存获益。需要进一步研究以优化治疗序贯方案，并探索输注时机在ICI策略中的影响。
肿瘤(癌症)患者之家