avelumab 维持治疗用于一线诱导化疗后与继续化疗相比用于胃癌患者的 III 期临床试验：JAVELIN Gastric 100 的结果。

Phase III Trial of Avelumab Maintenance After First-Line Induction Chemotherapy Versus Continuation of Chemotherapy in Patients With Gastric Cancers: Results From JAVELIN Gastric 100.

机构信息

Department of Internal Medicine, Johannes-Gutenberg University, Mainz, Germany.

Department of Oncology, Budgetary Healthcare Institution of Omsk Region Clinical Oncology Dispensary, Omsk, Russian Federation.

出版信息

J Clin Oncol. 2021 Mar 20;39(9):966-977. doi: 10.1200/JCO.20.00892. Epub 2020 Nov 16.

PURPOSE

The role of maintenance therapy for gastric (GC) or gastroesophageal junction cancer (GEJC) is unclear. We investigated avelumab (anti-programmed death ligand-1 [PD-L1]) maintenance after first-line induction chemotherapy for GC/GEJC.

PATIENTS AND METHODS

JAVELIN Gastric 100 was a global, open-label, phase III trial. Eligible patients had untreated, unresectable, human epidermal growth factor receptor 2-negative, locally advanced or metastatic GC or GEJC. Patients without progressive disease after 12 weeks of first-line chemotherapy with oxaliplatin plus a fluoropyrimidine were randomly assigned 1:1 to avelumab 10 mg/kg every 2 weeks or continued chemotherapy, stratified by region (Asia non-Asia). The primary end point was overall survival (OS) after induction chemotherapy in all randomly assigned patients or the PD-L1-positive randomly assigned population (≥ 1% of tumor cells; 73-10 assay).

RESULTS

A total of 805 patients received induction; 499 were randomly assigned to avelumab (n = 249) or continued chemotherapy (n = 250). Median OS was 10.4 months (95% CI, 9.1 to 12.0 months) versus 10.9 months (95% CI, 9.6 to 12.4 months) and 24-month OS rate was 22.1% versus 15.5% with avelumab versus chemotherapy, respectively (hazard ratio [HR], 0.91; 95% CI, 0.74 to 1.11; = .1779). In the PD-L1-positive population (n = 54), the HR for OS was 1.13 (95% CI, 0.57 to 2.23; = .6352). In an exploratory analysis of the PD-L1-positive population, defined as combined positive score ≥ 1 (22C3 assay; n = 137), median OS was 14.9 months (95% CI, 8.7 to 17.3 months) with avelumab versus 11.6 months (95% CI, 8.4 to 12.6 months) with chemotherapy (unstratified HR, 0.72; 95% CI, 0.49 to 1.05). With avelumab and chemotherapy, treatment-related adverse events (TRAEs) occurred in 149 (61.3%) and 184 (77.3%) patients, including grade ≥ 3 TRAEs in 31 (12.8%) and 78 (32.8%) patients, respectively.

CONCLUSION

JAVELIN Gastric 100 did not demonstrate superior OS with avelumab maintenance versus continued chemotherapy in patients with advanced GC or GEJC overall or in a prespecified PD-L1-positive population.

目的

胃癌（GC）或胃食管结合部癌（GEJC）维持治疗的作用尚不明确。我们研究了avelumab（抗程序性死亡配体-1 [PD-L1]）在一线诱导化疗后用于 GC/GEJC 的维持治疗。

患者和方法

JAVELIN Gastric 100 是一项全球性、开放性、III 期临床试验。符合条件的患者为未经治疗、不可切除、人表皮生长因子受体 2 阴性、局部晚期或转移性 GC 或 GEJC。在接受 12 周含奥沙利铂和氟嘧啶的一线化疗后无疾病进展的患者，按区域（亚洲非亚洲）以 1:1 的比例随机分配接受avelumab 10 mg/kg 每 2 周或继续化疗。主要终点为所有随机分配患者或 PD-L1 阳性随机分配人群（≥肿瘤细胞的 1%；73-10 检测）的诱导化疗后的总生存期（OS）。

结果

共 805 例患者接受了诱导治疗；499 例患者被随机分配至avelumab 组（n = 249）或继续化疗组（n = 250）。中位 OS 为 10.4 个月（95%CI，9.1 至 12.0 个月）与 10.9 个月（95%CI，9.6 至 12.4 个月），avelumab 组和化疗组 24 个月 OS 率分别为 22.1%和 15.5%（风险比 [HR]，0.91；95%CI，0.74 至 1.11；=.1779）。在 PD-L1 阳性人群（n = 54）中，OS 的 HR 为 1.13（95%CI，0.57 至 2.23；=.6352）。在 PD-L1 阳性人群（定义为联合阳性评分≥1（22C3 检测）；n = 137）的探索性分析中，avelumab 组中位 OS 为 14.9 个月（95%CI，8.7 至 17.3 个月），化疗组为 11.6 个月（95%CI，8.4 至 12.6 个月）（未分层 HR，0.72；95%CI，0.49 至 1.05）。avelumab 组和化疗组分别有 149（61.3%）和 184（77.3%）例患者发生治疗相关不良事件（TRAEs），包括 31（12.8%）和 78（32.8%）例患者发生≥3 级 TRAEs。