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ASCO年会于5月29日—6月2日在美国芝加哥召开。5月31日上午的消化系统（非结直肠）肿瘤口头报告专场上，一项摘要号为4001的试验，在经抗-PD-1单克隆抗体pembrolizumab（MK-3475）治疗的，晚期胃癌患者中，评估了PD-L1表达和临床预后之间的关系。医脉通整理如下：
肿瘤利用PD-1通路逃避免疫监视。pembrolizumab是一种抗PD-1单克隆抗体，在晚期肿瘤中已经显示出抗肿瘤活性。研究人员通过Keynote-012试验，对pembrolizumab治疗晚期胃癌的安全性和有效性进行评估。
这项研究采用标准免疫组化方法（IHC）通过22C3抗体对来自于亚太（AP）和世界其他地区（ROW）保存的复发/晚期胃或胃食管交接区腺癌患者的肿瘤标本筛选PD-L1的表达。研究纳入了基质鲜明或癌细胞巢PD-L1染色≥1%的患者。Pembrolizumab的给药方案为10mg/kg，每2周重复，持续用药24个月或直至出现完全缓解，疾病进展或无法耐受的毒副反应。每8周进行影像学检查。
该研究主要疗效终点是客观反应率（ORR），该研究采用RECIST1.1标准，评定结果经独立中心复审。次要终点包括疗效持续时间，无病生存期（PFS）和总生存期（OS）。
在162例筛选患者中，有65（40%）为PD-L1+。这65例患者中，有39例纳入了研究（AP 19例，ROW 20例，中位年龄63岁[范围，33-78]）。晚期患者既往接受的疗程数为0至5不等；其中2个疗程治疗以上的患者占67%。中位随访时间为8.8个月（6.2-12.6），其中13名（33%）患者仍在治疗中。
在试验过程中，有四例患者发生3-5级（最高等级为5级）药物相关不良反应，具体为周围感觉神经病变，乏力，食欲下降，缺氧，肺炎（各1例）。药物相关性死亡（缺氧）1例。中心复查结果ORR为22%（95%CI，10-39），研究者评定结果ORR为33%（95%CI，19-50）。中位时间起效时间为8周（范围7-16），中位疗效持续时间为24周（范围8+至33+）。PD-L1的表达水平与ORR相关（单侧P=0.10）。6个月的PFS率为24%。6个月的OS率为69%。
综上所述，本项研究发现pembrolizumab在晚期胃癌中表现出可观的抗肿瘤活性和可处理的治疗相关毒副反应。这些结果为pembrolizumab治疗胃癌研究的进一步开展提供了支持。临床试验信息：NCT01848834。
阅读原文摘要
Relationship between PD-L1 expression and clinical outcomes in patients with advanced gastric cancer treated with the anti-PD-1 monoclonal antibody pembrolizumab (MK-3475) in KEYNOTE-012.（Abstract 4001）
Authors：Yung-Jue Bang, Hyun-Choel Chung,et al.
Session Type：Oral Abstract Session
Background：Tumors use the PD-1 pathway to evade immune surveillance. Pembrolizumab, an anti–PD-1 monoclonal antibody, has shown antitumor activity in advanced cancers. We assessed the safety and efficacy of pembrolizumab in patients with advanced gastric cancer in KEYNOTE-012 (Clinicaltrials.gov identifier, NCT01848834).
Methods：Archival tumor samples from patients from Asia-Pacific (AP) and rest of the world (ROW) with recurrent or metastatic adenocarcinoma of the stomach or gastroesophageal junction were screened for PD-L1 expression using a prototype IHC assay with the 22C3 antibody. Only patients with distinctive stromal or ≥ 1% tumor nest cell PD-L1 staining were eligible. Patients received pembrolizumab 10 mg/kg every 2 weeks for up to 24 months or until complete response, progression, or unacceptable toxicity. Imaging was performed every 8 weeks. Primary efficacy end point is ORR assessed per RECIST v1.1 by independent central review. Secondary end points include duration of response, PFS, and OS.
Results：Of the 162 patients screened, 65 (40%) were PD-L1+. Of these 65 patients, 39 enrolled (19 from AP, 20 from ROW; median age, 63 years [range, 33-78]). The number of prior therapies for advanced disease ranged from 0 to 5; 67% received ≥ 2 prior therapies. Median follow-up duration was 8.8 months (range, 6.2-12.6); 13 patients (33%) remain on therapy. Four patients experienced 5 total grade 3-5 drug-related adverse events: peripheral sensory neuropathy, fatigue, decreased appetite, hypoxia, and pneumonitis (n = 1 each). There was 1 drug-related death (hypoxia). ORR was 22% (95% CI, 10-39) by central review and 33% (95% CI, 19-50) by investigator review. Median time to response was 8 weeks (range, 7-16), with a median response duration of 24 weeks (range, 8+ to 33+). PD-L1 expression level was associated with ORR (1-sided P = 0.10). The 6-month PFS rate was 24%. The 6-month OS rate was 69%.
Conclusions：Pembrolizumab demonstrated manageable toxicity and promising antitumor activity in advanced gastric cancer. These results support the ongoing development of pembrolizumab for gastric cancer. Clinical trial information: NCT01848834.
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