avelumab 对比医师选择的化疗作为晚期胃癌或胃食管结合部癌三线治疗的 III 期随机试验：JAVELIN Gastric 300 的主要分析结果
Phase III, randomised trial of avelumab versus physician's choice of chemotherapy as third-line treatment of patients with advanced gastric or gastro-oesophageal junction cancer: primary analysis of JAVELIN Gastric 300.
机构信息
Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea.
Universidad de la Frontera, Temuco, Chile.
出版信息
Ann Oncol. 2018 Oct 1;29(10):2052-2060. doi: 10.1093/annonc/mdy264.
BACKGROUND
There currently are no internationally recognised treatment guidelines for patients with advanced gastric cancer/gastro-oesophageal junction cancer (GC/GEJC) in whom two prior lines of therapy have failed. The randomised, phase III JAVELIN Gastric 300 trial compared avelumab versus physician's choice of chemotherapy as third-line therapy in patients with advanced GC/GEJC.
PATIENTS AND METHODS
Patients with unresectable, recurrent, locally advanced, or metastatic GC/GEJC were recruited at 147 sites globally. All patients were randomised to receive either avelumab 10 mg/kg by intravenous infusion every 2 weeks or physician's choice of chemotherapy (paclitaxel 80 mg/m2 on days 1, 8, and 15 or irinotecan 150 mg/m2 on days 1 and 15, each of a 4-week treatment cycle); patients ineligible for chemotherapy received best supportive care. The primary end point was overall survival (OS). Secondary end points included progression-free survival (PFS), objective response rate (ORR), and safety.
RESULTS
A total of 371 patients were randomised. The trial did not meet its primary end point of improving OS {median, 4.6 versus 5.0 months; hazard ratio (HR)=1.1 [95% confidence interval (CI) 0.9-1.4]; P = 0.81} or the secondary end points of PFS [median, 1.4 versus 2.7 months; HR=1.73 (95% CI 1.4-2.2); P > 0.99] or ORR (2.2% versus 4.3%) in the avelumab versus chemotherapy arms, respectively. Treatment-related adverse events (TRAEs) of any grade occurred in 90 patients (48.9%) and 131 patients (74.0%) in the avelumab and chemotherapy arms, respectively. Grade ≥3 TRAEs occurred in 17 patients (9.2%) in the avelumab arm and in 56 patients (31.6%) in the chemotherapy arm.
CONCLUSIONS
Treatment of patients with GC/GEJC with single-agent avelumab in the third-line setting did not result in an improvement in OS or PFS compared with chemotherapy. Avelumab showed a more manageable safety profile than chemotherapy.
TRIAL REGISTRATION
ClinicalTrials.gov: NCT02625623.
背景
目前尚无针对二线治疗失败的晚期胃/胃食管交界癌（GC/GEJC）患者的国际公认治疗指南。随机、III 期 JAVELIN Gastric 300 试验比较了avelumab 与化疗作为三线治疗在晚期 GC/GEJC 患者中的疗效。
方法
全球 147 个地点招募了不可切除、复发、局部晚期或转移性 GC/GEJC 患者。所有患者均随机接受avelumab 10mg/kg 静脉输注，每 2 周 1 次或化疗（紫杉醇 80mg/m2，第 1、8 和 15 天或伊立替康 150mg/m2，每 4 周治疗周期的第 1 和 15 天）；不适合化疗的患者接受最佳支持治疗。主要终点是总生存期（OS）。次要终点包括无进展生存期（PFS）、客观缓解率（ORR）和安全性。
结果
共随机分配了 371 名患者。试验未达到改善 OS 的主要终点[中位数，4.6 与 5.0 个月；风险比（HR）=1.1[95%置信区间（CI）0.9-1.4]；P=0.81]或次要终点 PFS[中位数，1.4 与 2.7 个月；HR=1.73（95% CI 1.4-2.2）；P>0.99]或 ORR（分别为 2.2%与 4.3%）。avelumab 组和化疗组分别有 90 例（48.9%）和 131 例（74.0%）患者出现任何等级的治疗相关不良事件（TRAEs）。avelumab 组有 17 例（9.2%）和化疗组有 56 例（31.6%）患者发生≥3 级 TRAEs。
结论
与化疗相比，三线治疗晚期 GC/GEJC 患者时，单药avelumab 治疗并未改善 OS 或 PFS。avelumab 的安全性优于化疗。
试验注册
ClinicalTrials.gov：NCT02625623。
Zotero 插件