Consensus of Chinese experts on detection of HER-2 in gastroscopic biopsy specimens of gastric cancer (2023 edition)
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摘要: 胃癌是最常见的消化道恶性肿瘤之一。人表皮生长因子受体-2（human epidermal growth factor receptor-2，HER-2）是胃癌（包括胃食管结合部腺癌）临床治疗的重要靶点。规范、准确的胃镜活检标本HER2表达状态检测对于胃癌分子分型与选择抗HER-2靶向药物治疗具有重要意义。本共识基于循证医学证据和国际通行的Delphi法，在胃镜活检标本HER-2检测的临床意义、适用人群、活检操作规范、标本前期处理、检测方法、检测质量控制与多学科合作等方面达成初步统一，以期对临床工作提供指导。
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关键词:
- 胃癌 /
- 人表皮生长因子受体-2 /
- 胃镜活检 /
- 专家共识
Abstract: Gastric cancer is one of the most common malignant tumors of the digestive tract. Human epidermal growth factor receptor-2 (HER-2) is an important target for clinical treatment of gastric cancer (including gastroesophageal junction adenocarcinoma). Standardized and accurate detection of HER-2 expression in gastroscopic biopsy specimens is vitally important for molecular typing of gastric cancer and selection of anti-HER-2 targeted drug therapy. Preliminary consensuses, based on medical evidence and the internationally accepted Delphi method, have been reached on the clinical significance, applicable population, biopsy operation specifications, specimen pretreatment, detection method, detection quality control, and multidisciplinary cooperation on the HER-2 detection of gastroscopic biopsy specimens. These consensuses will potentially provide guidance for clinical work. -
表 1 GRADE证据等级分级系统
等级 内容 高（A） Ⅰ级：进一步研究几乎不可能改变对临床疗效评估结果的可信度，为高级别证据 中（B） Ⅱ级：进一步研究有可能对疗效评估结果的可信度有重要影响，且有可能改变评估结果，为中级别证据 低（C） Ⅲ级：进一步研究很有可能对疗效评估结果的可信度有重要影响，且极有可能改变评估结果，为低级别证据 极低（D） Ⅳ级：任何疗效评估结果均不确定，为极低级别证据 
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表 2 HER-2阳性晚期胃癌抗HER-2治疗临床研究
研究名称 研究类型 治疗线数（线） 治疗方案 mOS（月） mPFS（月） ORR ToGA[5] Ⅲ期 一 曲妥珠单抗+化疗 vs. 化疗 13.8 vs. 11.1 6.7 vs. 5.5 47% vs. 35% DESTINY-Gastric01[21] Ⅱ期 三 德曲妥珠单抗 vs. 医生选择的化疗
（伊立替康或紫杉醇）12.5 vs. 8.4 5.6 vs. 3.5 43% vs. 12% DESTINY-Gastric02[22] Ⅱ期 二 德曲妥珠单抗 12.1 5.6 42% C008[23] Ⅱ期 三 维迪西妥单抗 7.9 4.1 24.8% KEYNOTE-811[24] Ⅲ期 一 帕博利珠单抗+曲妥珠单抗+化疗 vs.
曲妥珠单抗+化疗— — 74.4% vs. 51.9%
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表 3 HER-2阳性胃癌围手术期抗HER-2治疗临床研究
研究名称 研究类型 入组人群 治疗方案 pCR（%） R0切除率（%） mDFS（月） mOS（月） NEOHX[25] Ⅱ期 HER-2阳性 GC/GEJC患者（T1-2N+M0 或 T3-4NxM0） 曲妥珠单抗+XELOX围手术期治疗 9.6% 90% 18个月DFS率71%；24个月DFS率60% mOS为79.9个月； 5年OS率58.0% HER-FLOT[26] Ⅱ期 HER-2阳性 GC/GEJC患者 （≥cT2 或 cN+） 曲妥珠单抗+FLOT围手术期治疗 21.4% 92.9% 42.5个月 3年OS率82.1% PETRARCA[27] Ⅱ/Ⅲ期 HER-2阳性GC/GEJC患者 （cT2-4 cNany cM0或cTany cN+ cM0） 曲妥珠单抗+帕妥珠单抗+FLOT vs. FLOT 围手术期治疗 35% vs. 12% 93% vs. 90% 2年DFS率70% vs. 54% 2年OS率84% vs. 77% INNOVATION[28] Ⅱ期 HER-2阳性GC/GEJC患者
（第7版UICC TNM Ib～Ⅲ期）曲妥珠单抗+帕妥珠单抗+化疗 vs. 曲妥珠单抗+化疗 vs. 化疗围手术期治疗 MPR 26.4% vs. 37.0% vs. 23.3% 85.9% vs. 90.3% vs. 83.9% — — He等[29] 回顾性研究 HER-2阳性局部进展期GC/GEJC患者 曲妥珠单抗+化疗 vs. 化疗新辅助 14.7% vs. 2.6% — — —
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