Hoffman-Censits J, Tsiatas M, Chang P M-H, Kim M, Antonuzzo L, Shin S J, Gakis G, Blais N, Kim S H, Smith A, Arranz Arija J A, Su Y L, Zagouri F, Maruzzo M, Tournigand C, Forget F, Schneider A, Tyroller K, Jacob N, Grivas P, Valderrama B P
Department of Medical Oncology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Johns Hopkins Medical Institutions, Baltimore, USA; Department of Urology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Johns Hopkins Medical Institutions, Baltimore, USA.
Department of Medical Oncology, Athens Medical Center, Marousi, Greece.
Ann Oncol. 2025 Sep;36(9):1088-1095. doi: 10.1016/j.annonc.2025.05.010. Epub 2025 Jun 1.
Avelumab first-line maintenance is a recommended treatment option for patients with locally advanced or metastatic urothelial carcinoma (la/mUC) without progression following platinum-based chemotherapy (PBC). The JAVELIN Bladder Medley phase II trial is investigating the efficacy and safety of maintenance treatment with avelumab combined with other antitumor agents versus avelumab monotherapy. We report an interim analysis of avelumab plus sacituzumab govitecan (SG) versus avelumab monotherapy.
Patients with la/mUC without progression after first-line PBC were randomized 2 : 1 to receive avelumab (800 mg every 2 weeks) plus SG (10 mg/kg on days 1 and 8 of 21-day cycles) or avelumab monotherapy (800 mg every 2 weeks). Primary endpoints are investigator-assessed progression-free survival (PFS) and safety. For PFS and overall survival (OS), data in the avelumab monotherapy arm were extended per protocol using propensity score-weighted JAVELIN Bladder 100 data.
At data cut-off (16 September 2024), 38/74 patients (51.4%) in the avelumab plus SG arm and 10/37 patients (27.0%) in the avelumab monotherapy arm were still receiving study treatment. Median PFS with avelumab plus SG versus avelumab monotherapy was 11.17 versus 3.75 months, respectively [hazard ratio (HR) 0.49, 95% confidence interval (CI) 0.31-0.76; prespecified efficacy boundary: HR ≤ 0.60]. OS data were immature; median OS was not reached versus 23.75 months, respectively (HR 0.79, 95% CI 0.42-1.50). In patients treated with avelumab plus SG or avelumab monotherapy, any-grade treatment-related adverse events (TRAEs) occurred in 97.3% versus 63.9% (grade ≥3 in 69.9% versus 0%), respectively.
In patients with la/mUC without progression after first-line PBC, PFS was prolonged with avelumab plus SG versus avelumab monotherapy as maintenance treatment. TRAEs were more frequent with the combination and were consistent with known safety profiles of SG and avelumab. Combining avelumab with anti-Trop-2 antibody-drug conjugates may be a promising strategy to improve patient outcomes in la/mUC.
阿维鲁单抗一线维持治疗是局部晚期或转移性尿路上皮癌（la/mUC）患者在铂类化疗（PBC）后未进展时的推荐治疗选择。JAVELIN Bladder Medley II期试验正在研究阿维鲁单抗联合其他抗肿瘤药物与阿维鲁单抗单药维持治疗的疗效和安全性。我们报告了阿维鲁单抗联合赛托珠单抗戈维汀（SG）与阿维鲁单抗单药治疗的中期分析结果。
一线PBC后未进展的la/mUC患者按2:1随机分组，分别接受阿维鲁单抗（每2周800mg）联合SG（在21天周期的第1天和第8天给予10mg/kg）或阿维鲁单抗单药治疗（每2周800mg）。主要终点是研究者评估的无进展生存期（PFS）和安全性。对于PFS和总生存期（OS），使用倾向评分加权的JAVELIN Bladder 100数据按方案扩展了阿维鲁单抗单药治疗组的数据。
在数据截止时（2024年9月16日），阿维鲁单抗联合SG组的38/74例患者（51.4%）和阿维鲁单抗单药治疗组的10/37例患者（27.0%）仍在接受研究治疗。阿维鲁单抗联合SG与阿维鲁单抗单药治疗的中位PFS分别为11.17个月和3.75个月[风险比（HR）0.49，95%置信区间（CI）0.31 - 0.76；预设疗效界值：HR≤0.60]。OS数据不成熟；分别为未达到中位OS和23.75个月（HR 0.79，95% CI 0.42 - 1.50）。在接受阿维鲁单抗联合SG或阿维鲁单抗单药治疗的患者中，任何级别的治疗相关不良事件（TRAEs）分别发生在97.3%和63.9%（≥3级分别为69.9%和0%）。
在一线PBC后未进展的la/mUC患者中，阿维鲁单抗联合SG作为维持治疗比阿维鲁单抗单药治疗延长了PFS。联合治疗的TRAEs更频繁，且与SG和阿维鲁单抗已知的安全性特征一致。将阿维鲁单抗与抗Trop-2抗体药物偶联物联合使用可能是改善la/mUC患者预后的一种有前景的策略。
