Fred Hutchinson Cancer Center, University of Washington, Seattle, WA, USA.
Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Eur Urol. 2023 Jul;84(1):95-108. doi: 10.1016/j.eururo.2023.03.030. Epub 2023 Apr 28.
In the phase 3 JAVELIN Bladder 100 trial, avelumab first-line (1L) maintenance + best supportive care (BSC) significantly prolonged overall survival (OS) and progression-free survival (PFS) versus BSC alone in patients with advanced urothelial carcinoma (aUC) who were progression-free following 1L platinum-based chemotherapy, leading to regulatory approval in various countries.
To analyze clinically relevant subgroups from JAVELIN Bladder 100.
DESIGN, SETTING, AND PARTICIPANTS: Patients with unresectable locally advanced or metastatic UC without progression on 1L gemcitabine + cisplatin or carboplatin were randomized to receive avelumab + BSC (n = 350) or BSC alone (n = 350). Median follow-up was >19 mo in both arms (data cutoff October 21, 2019). This trial is registered on ClinicalTrials.gov as NCT02603432.
OS (primary endpoint) and PFS were analyzed in protocol-specified and post hoc subgroups using the Kaplan-Meier method and Cox proportional hazards models.
Hazard ratios (HRs) for OS with avelumab + BSC versus BSC alone were <1.0 across all subgroups examined, including patients treated with 1L cisplatin + gemcitabine (HR 0.69, 95% confidence interval [CI] 0.50-0.93) or carboplatin + gemcitabine (HR 0.64, 95% CI 0.46-0.90), patients with PD-L1 tumors treated with carboplatin + gemcitabine (HR 0.67, 95% CI 0.39-1.14), and patients whose best response to chemotherapy was a complete response (HR 0.80, 95% CI 0.46-1.37), partial response (HR 0.62, 95% CI 0.46-0.84), or stable disease (HR 0.70, 95% CI 0.46-1.06). Observations were similar for PFS. Limitations include the smaller size and post hoc evaluation without multiplicity adjustment for some subgroups.
Analyses of OS and PFS in clinically relevant subgroups were consistent with results for the overall population, further supporting avelumab 1L maintenance as standard-of-care treatment for patients with aUC who are progression-free following 1L platinum-based chemotherapy.
In the JAVELIN Bladder 100 study, maintenance treatment with avelumab helped many different groups of people with advanced cancer of the urinary tract to live longer.
在 3 期 JAVELIN Bladder 100 试验中，avelumab 一线（1L）维持治疗+最佳支持治疗（BSC）与单独 BSC 相比，显著延长了晚期尿路上皮癌（aUC）患者的总生存期（OS）和无进展生存期（PFS），这些患者在接受 1L 基于铂类的化疗后无进展，在多个国家获得了监管批准。
分析 JAVELIN Bladder 100 中的临床相关亚组。
设计、地点和参与者：未接受局部晚期或转移性 UC 手术切除且在 1L 吉西他滨+顺铂或卡铂治疗后无进展的患者被随机分配接受avelumab+BSC（n=350）或单独 BSC（n=350）。两组的中位随访时间均>19 个月（数据截止日期为 2019 年 10 月 21 日）。该试验在 ClinicalTrials.gov 上注册为 NCT02603432。
使用 Kaplan-Meier 方法和 Cox 比例风险模型分析了方案规定和事后亚组中的 OS（主要终点）和 PFS。
avelumab+BSC 与单独 BSC 相比，OS 的风险比（HR）在所有检查的亚组中均<1.0，包括接受 1L 顺铂+吉西他滨（HR 0.69，95%置信区间 [CI] 0.50-0.93）或卡铂+吉西他滨（HR 0.64，95% CI 0.46-0.90）治疗的患者、接受卡铂+吉西他滨治疗的 PD-L1 肿瘤患者（HR 0.67，95% CI 0.39-1.14）、以及化疗最佳反应为完全缓解（HR 0.80，95% CI 0.46-1.37）、部分缓解（HR 0.62，95% CI 0.46-0.84）或稳定疾病（HR 0.70，95% CI 0.46-1.06）的患者。PFS 的观察结果相似。局限性包括某些亚组的样本量较小且事后评估，没有进行多重性调整。
对临床相关亚组的 OS 和 PFS 的分析结果与总体人群一致，进一步支持 avelumab 1L 维持治疗作为接受过 1L 基于铂类化疗后无进展的 aUC 患者的标准治疗。
在 JAVELIN Bladder 100 研究中，avelumab 的维持治疗帮助了许多不同类型的晚期膀胱癌患者活得更久。
