Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
Department not applicable, Hemato-oncology Clinic (A) Pvt. Ltd., HOC Vedanta, Ahmedabad, India.
Urol Oncol. 2023 May;41(5):256.e17-256.e25. doi: 10.1016/j.urolonc.2023.02.002. Epub 2023 Apr 3.
The phase 3 JAVELIN Bladder 100 trial showed significantly prolonged overall survival (OS) with avelumab first-line maintenance + best supportive care (BSC) vs. BSC alone in patients with advanced urothelial carcinoma (UC) that had not progressed with first-line platinum-containing chemotherapy. Here, efficacy and safety were assessed from the initial analysis of the JAVELIN Bladder 100 trial (data cutoff October 21, 2019) in patients enrolled in Asian countries.
Patients with locally advanced or metastatic UC that had not progressed with 4 to 6 cycles of first-line platinum-containing chemotherapy (gemcitabine + cisplatin or carboplatin) were randomized 1:1 to receive avelumab first-line maintenance + BSC or BSC alone, stratified by best response to first-line chemotherapy and visceral vs. nonvisceral disease when initiating first-line chemotherapy. The primary endpoint was OS assessed from randomization in all patients and patients with PD-L1+ tumors (Ventana SP263 assay). Secondary endpoints included progression-free survival (PFS) and safety.
A total of 147 patients in JAVELIN Bladder 100 were enrolled in Asian countries (Hong Kong, India, Japan, South Korea, and Taiwan). In this Asian subgroup, 73 and 74 patients received avelumab + BSC or BSC alone, respectively. Median OS was 25.3 months (95% CI, 18.6 to not estimable [NE]) in the avelumab + BSC arm vs. 18.7 months (95% CI, 12.8-NE) in the BSC alone arm (hazard ratio [HR], 0.74 [95% CI, 0.43-1.26]); median PFS was 5.6 months (95% CI, 2.0-7.5) vs. 1.9 months (95% CI, 1.9-1.9), respectively (HR, 0.58 [95% CI, 0.38-0.86]). In the avelumab + BSC vs. BSC alone arms, grade ≥3 treatment-emergent adverse events (any causality) occurred in 44.4% vs. 16.2%, respectively. The most common grade ≥3 treatment-emergent adverse events in the avelumab + BSC arm were anemia (9.7%), amylase increased (5.6%), and urinary tract infection (4.2%).
Efficacy and safety results for avelumab first-line maintenance in the Asian subgroup of JAVELIN Bladder 100 were generally consistent with those in the overall trial population. These data support the use of avelumab first-line maintenance as standard of care for Asian patients with advanced UC that has not progressed with first-line platinum-containing chemotherapy. NCT02603432.
在 III 期 JAVELIN Bladder 100 试验中，与单独最佳支持治疗（BSC）相比，avelumab 一线维持治疗联合 BSC 显著延长了局部晚期或转移性尿路上皮癌（UC）患者的总生存期（OS），这些患者在接受一线含铂化疗后未进展。在此，对来自在亚洲国家入组患者的 JAVELIN Bladder 100 试验初始分析（数据截止日期 2019 年 10 月 21 日）的疗效和安全性进行评估。
未接受过 4-6 周期一线含铂化疗（吉西他滨+顺铂或卡铂）的局部晚期或转移性 UC 患者按最佳一线化疗缓解情况和一线化疗起始时是否存在内脏或非内脏疾病进行 1:1 随机分组，分别接受 avelumab 一线维持治疗联合 BSC 或单独 BSC。所有患者和 PD-L1+肿瘤患者（Ventana SP263 检测）的主要终点为随机分组后的 OS。次要终点包括无进展生存期（PFS）和安全性。
在 JAVELIN Bladder 100 中，共有 147 例患者在亚洲国家（中国香港、印度、日本、韩国和中国台湾）入组。在这个亚洲亚组中，分别有 73 例和 74 例患者接受了 avelumab+BSC 或单独 BSC。avelumab+BSC 组的中位 OS 为 25.3 个月（95%CI，18.6-NE），单独 BSC 组为 18.7 个月（95%CI，12.8-NE）（HR，0.74 [95%CI，0.43-1.26]）；中位 PFS 分别为 5.6 个月（95%CI，2.0-7.5）和 1.9 个月（95%CI，1.9-1.9）（HR，0.58 [95%CI，0.38-0.86]）。avelumab+BSC 组与单独 BSC 组分别有 44.4%和 16.2%的患者发生任何病因导致的≥3 级治疗相关不良事件。avelumab+BSC 组最常见的≥3 级治疗相关不良事件为贫血（9.7%）、淀粉酶升高（5.6%）和尿路感染（4.2%）。
JAVELIN Bladder 100 亚洲亚组中 avelumab 一线维持治疗的疗效和安全性结果与总体试验人群基本一致。这些数据支持在亚洲地区，对于未接受过一线含铂化疗的晚期 UC 患者，用 avelumab 一线维持治疗作为标准治疗方案。NCT02603432。
