HER-2阳性晚期胃癌免疫治疗临床分析

  目的  分析程序性细胞死亡受体-1（programmed cell death protein 1，PD-1）单抗联合曲妥珠单抗标准治疗在一线HER-2阳性晚期胃癌的临床疗效及安全性。  方法  选取2019年6月至2021年6月河南省肿瘤医院HER-2阳性晚期胃癌患者110例，根据治疗方法分为研究组（48例）和对照组（62例），比较两组患者临床疗效及安全性。  结果  中位随访时间14.2个月，研究组和对照组客观缓解率（overall response rate，ORR）分别为41.7%和37.1%，疾病控制率（disease controlrate，DCR）分别为87.5%和80.6%，中位无进展生存期（median progression-free survival，mPFS）分别为9.2个月和6.8个月（HR=0.624，95%CI:0.396～0.981；P=0.046）。两组患者免疫组织化学（immunohistochemistry， IHC) 3+的mPFS分别为11.6个月和6.8个月（HR=0.461，95%CI:0.260～0.817；P=0.012），其中研究组IHC3+和IHC2+（in situ hybridization positive，ISH阳性）的mPFS分别为11.6个月和7.8个月（HR=0.486，95%CI:0.215～1.097；P=0.051），研究组中程序性细胞死亡配体1（programmed cell death-ligand 1，PD-L1）阳性和PD-L1阴性的mPFS分别为9.2个月和4.9个月（HR=0.370，95%CI:0.104～1.322；P=0.033）。研究组和对照组所有不良反应事件中，甲状腺功能减退（P=0.034）及中性粒细胞减少（P=0.046）差异具有统计学意义。多因素分析显示，ECOG评分、腹膜转移及治疗方案是PFS独立影响因素（均P<0.05）。  结论  免疫联合曲妥珠单抗标准方案治疗HER-2阳性晚期胃癌具有良好临床疗效，可延长患者PFS，IHC3+患者免疫联合治疗效果可能更佳，且安全性可控。 

Clinical analysis of immunotherapy efficacy for HER-2-positive advanced gastric cancer

  Objective  To analyze the clinical efficacy and safety of programmed cell death protein 1 (PD-1) monotherapy combined with trastuzumab standard treatment as the first-line treatment for human epidermal growth factor receptor-2 (HER-2)-positive advanced gastric cancer (GC).   Methods  A total of 110 patients with HER-2-positive advanced GC who were enrolled in Henan Cancer Hospital from June 2019 to June 2021 were assigned into study group (n=48) and control group (n=62) according to the treatment methods, and the clinical efficacy and safety of the two groups were compared.  Results  The median follow-up time was 14.2 months. The study group showed better results compared to the control group in terms of objective response rate (ORR) (41.7% vs.37.1%), disease control rate (DCR) (87.5% vs. 80.6%), and the median progression-free survival (mPFS) (9.2 months vs.6.8 months) (HR=0.624, 95%CI: 0.396-0.981, P=0.046). The mPFS of IHC3+ in the study group and control group was 11.6 months vs. 6.8 months (HR=0.461, 95%CI: 0.260-0.817, P=0.012), mPFS of IHC3+ and IHC2+ (ISH positive) in the study group was 11.6 months vs.7.8 months (HR=0.486, 95%CI: 0.215-1.097, P=0.051), and the mPFS of PD-L1 positive and PD-L1 negative patients in the study group was 9.2 months vs.4.9 months (HR=0.370, 95%CI: 0.104-1.322, P=0.033). Only hypothyroidism (P=0.034) and neutropenia (P=0.046) were statistically different in all adverse events between the study group and control group. Multivariate analysis showed that ECOG score, peritoneal metastasis, and treatment regimens were independent factors of PFS (P<0.05).   Conclusions  Immunotherapy combined with trastuzumab standard treatment of HER-2-positive advanced gastric adenocarcinoma has good clinical efficacy and can prolong PFS. The effect of the immune combination treatment may be better with IHC3+ patients, and treatment safety is controllable.