avelumab（抗 PD-L1）作为晚期胃癌或胃食管结合部癌一线切换维持或二线治疗：JAVELIN 实体瘤试验的 1b 期结果。
Avelumab (anti-PD-L1) as first-line switch-maintenance or second-line therapy in patients with advanced gastric or gastroesophageal junction cancer: phase 1b results from the JAVELIN Solid Tumor trial.
机构信息
Yonsei Cancer Center, Yonsei University College of Medicine, Yonsei University Health System, Seoul, 03722, South Korea.
Sarah Cannon Research Institute/University College London, London, UK.
出版信息
J Immunother Cancer. 2019 Feb 4;7(1):30. doi: 10.1186/s40425-019-0508-1.
BACKGROUND
We evaluated the antitumor activity and safety of avelumab, a human anti-PD-L1 IgG1 antibody, as first-line switch-maintenance (1 L-mn) or second-line (2 L) treatment in patients with advanced gastric/gastroesophageal cancer (GC/GEJC) previously treated with chemotherapy.
METHODS
In a phase 1b expansion cohort, patients without (1 L-mn) or with (2 L) disease progression following first-line chemotherapy for advanced GC/GEJC received avelumab 10 mg/kg intravenously every 2 weeks. Endpoints included best overall response, progression-free survival (PFS), overall survival (OS), and safety.
RESULTS
Overall, 150 patients were enrolled (1 L-mn, n = 90; 2 L, n = 60) and median follow-up in the 1 L-mn and 2 L subgroups was 36.0 and 33.7 months, respectively. The confirmed objective response rate was 6.7% in both subgroups (95% CI, 2.5-13.9% and 1.8-16.2%, respectively), including complete responses in 2.2% of the 1 L-mn subgroup (n = 2). In the 1 L-mn and 2 L subgroups, median duration of response was 21.4 months (95% CI, 4.0-not estimable) and 3.5 months (95% CI, 2.8-8.3) and disease control rates were 56.7 and 28.3%, respectively. Median PFS in the 1 L-mn and 2 L subgroups was 2.8 months (95% CI, 2.3-4.1) and 1.4 months (95% CI, 1.3-1.5), with 6-month PFS rates of 23.0% (95% CI, 14.7-32.4%) and 7.9% (95% CI, 2.6-17.2%), and median OS was 11.1 months (95% CI, 8.9-13.7) and 6.6 months (95% CI, 5.4-9.4), respectively. In the 1 L-mn subgroup, median OS measured from start of 1 L chemotherapy was 18.7 months (95% CI, 15.4-20.6). Across both subgroups, 20.7% had an infusion-related reaction of any grade. Other common treatment-related adverse events (TRAEs) of any grade included fatigue (10.0%) and nausea (6.7%). Treatment-related serious adverse events occurred in 4.0% of patients. Overall, 8.7% had a grade ≥3 TRAE, including 1 treatment-related death.
CONCLUSION
Avelumab showed clinical activity and an acceptable safety profile in patients with GC/GEJC.
TRIAL REGISTRATION
ClinicalTrials.gov NCT01772004 ; registered 21 January 2013.
背景
我们评估了avelumab（一种人源抗 PD-L1 IgG1 抗体）在先前接受过化疗的晚期胃/胃食管交界癌（GC/GEJC）患者中的一线切换维持（1L-mn）或二线（2L）治疗的抗肿瘤活性和安全性。
方法
在 1b 期扩展队列中，在一线化疗后无疾病进展（1L-mn）或有疾病进展（2L）的患者接受avelumab 10mg/kg，每 2 周静脉注射一次。主要终点包括最佳总体反应、无进展生存期（PFS）、总生存期（OS）和安全性。
结果
共有 150 名患者入组（1L-mn，n=90；2L，n=60），1L-mn 和 2L 亚组的中位随访时间分别为 36.0 和 33.7 个月。两个亚组的确认客观缓解率均为 6.7%（95%CI，2.5-13.9%和 1.8-16.2%），包括 1L-mn 亚组 2.2%（n=2）的完全缓解。1L-mn 和 2L 亚组的中位缓解持续时间分别为 21.4 个月（95%CI，4.0-不可估计）和 3.5 个月（95%CI，2.8-8.3），疾病控制率分别为 56.7%和 28.3%。1L-mn 和 2L 亚组的中位 PFS 分别为 2.8 个月（95%CI，2.3-4.1）和 1.4 个月（95%CI，1.3-1.5），6 个月 PFS 率分别为 23.0%（95%CI，14.7-32.4%）和 7.9%（95%CI，2.6-17.2%），中位 OS 分别为 11.1 个月（95%CI，8.9-13.7）和 6.6 个月（95%CI，5.4-9.4）。在 1L-mn 亚组中，从 1L 化疗开始测量的中位 OS 为 18.7 个月（95%CI，15.4-20.6）。两个亚组均有 20.7%的患者发生任何等级的输注相关反应。其他常见的任何等级的治疗相关不良事件（TRAEs）包括疲劳（10.0%）和恶心（6.7%）。4.0%的患者发生了与治疗相关的严重不良事件。总体而言，8.7%的患者发生了 3 级以上 TRAE，包括 1 例治疗相关死亡。
结论
avelumab 在 GC/GEJC 患者中显示出临床活性和可接受的安全性。
试验注册
ClinicalTrials.gov NCT01772004；于 2013 年 1 月 21 日注册。
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