Zhang Lingyun, Guan Bin, Li Wei, Yu Shan, Li Qian, Yu Yiyi, Cui Yuehong, Sun Debin, Wang Yan
Department of Medical Oncology, Shanghai Geriatric Medical Center, Shanghai, China.
Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, China.
Transl Gastroenterol Hepatol. 2025 Apr 17;10:23. doi: 10.21037/tgh-24-95. eCollection 2025.
The prognosis of gastric cancer (GC) patients with human epidermal growth factor receptor 2 (HER2) positive was poor. To illustrate the underlying effective and distinctive molecular characteristics of programmed cell death protein 1 (PD-1) blockade in the treatment of GC with HER2 positive, we analyzed the survival outcome of PD-1 inhibitors combination regimen as the first-line treatment for GC patients with HER2-positive in China.
This retrospective real-world study compared the prognoses of first-line systemic treatment of PD-1 inhibitors combined with trastuzumab and chemotherapy (PTC group) and trastuzumab and chemotherapy (TC group) in Chinese patients with HER2-positive GC, and then further to identify the specific and molecular characteristics of PD-1 inhibitors treatment by hierarchical analysis. The patients were matched using propensity score matching (PSM). Overall survival (OS) and progression-free survival (PFS) were used as the primary and secondary endpoints of the study.
A total of 95 patients with HER2-positive GC receiving first-line treatment at Zhongshan Hospital of Fudan University from January 2019 to September 2022 were included. The median OS (24.67 16.00 months, P=0.01) and median PFS (15.57 7.57 months, P=0.008) of patients with HER2-positive GC who received PTC regimen were longer than those treated by TC regimen as first-line systemic treatment after PSM analysis. In hierarchical analysis, we discovered that programmed cell death ligand 1 (PD-L1) positive expression in tumor tissues was not a predictor of PD-1 inhibitors in HER2-positive GC. However, PD-L1 was an indicator of better survival outcomes by combined trastuzumab treatment in all GC patients. Furthermore, in the subgroup analysis, we found that the median OS for the PTC group was longer by nearly 8 months than the TC group in patients with HER2 gene copy number [HER2 fluorescence in situ hybridization (FISH) test] more than six, while the median OS for the PTC group was longer by approximately 12 months than the TC group in patients with HER2-positive GC with mutations.
The results suggested that patients with HER2-positive GC could benefit from PD-1 inhibitors combination with trastuzumab and chemotherapy, especially patients with HER-2 FISH more than six and mutations.
人表皮生长因子受体2（HER2）阳性的胃癌（GC）患者预后较差。为阐明程序性细胞死亡蛋白1（PD-1）阻断剂治疗HER2阳性GC的潜在有效且独特的分子特征，我们分析了在中国将PD-1抑制剂联合方案作为HER2阳性GC患者一线治疗的生存结果。
这项回顾性真实世界研究比较了中国HER2阳性GC患者中，PD-1抑制剂联合曲妥珠单抗及化疗（PTC组）与曲妥珠单抗及化疗（TC组）一线全身治疗的预后，然后通过分层分析进一步确定PD-1抑制剂治疗的特异性和分子特征。采用倾向评分匹配（PSM）对患者进行匹配。总生存期（OS）和无进展生存期（PFS）作为研究的主要和次要终点。
纳入了2019年1月至2022年9月在复旦大学附属中山医院接受一线治疗的95例HER2阳性GC患者。PSM分析后，接受PTC方案的HER2阳性GC患者的中位OS（24.67对16.00个月，P=0.01）和中位PFS（15.57对7.57个月，P=0.008）长于接受TC方案一线全身治疗的患者。在分层分析中，我们发现肿瘤组织中程序性细胞死亡配体1（PD-L1）阳性表达不是HER2阳性GC中PD-1抑制剂的预测指标。然而，在所有GC患者中，PD-L1是联合曲妥珠单抗治疗生存结果更好的一个指标。此外，在亚组分析中，我们发现HER2基因拷贝数[HER2荧光原位杂交（FISH）检测]大于6的患者中，PTC组的中位OS比TC组长近8个月，而HER2阳性且有特定突变的GC患者中，PTC组的中位OS比TC组长约12个月。
结果表明，HER2阳性GC患者可从PD-1抑制剂联合曲妥珠单抗及化疗中获益，尤其是HER-2 FISH大于6且有特定突变的患者。
